Biotech Start-ups Research Articles

Brazilian Northern biotech startups: an examination of supporting factors for web portal modeling

The purpose of this research project is to determine the elements that would facilitate the establishment of a biotechnology startup help site in the northern part of Brazil. As part of the research, data on startups was gathered, obstacles to growth were identified, and issues faced by the companies were noted. Based on the responses to the questionnaire, conclusions were made on the major difficulties these businesses encountered. The main barrier is found to be the difficulty in acquiring finance; other challenging elements include revenue generation and equipment availability. It is acknowledged that regional concerns, such input availability, and logistics, have a significant impact on the difficulties that local businesses encounter. Recommendations are made based on the challenges found to improve the startup growth environment, hence promoting sustainable innovation and the bioeconomy's development.

Rethinking new venture growth: A time series cluster analysis of biotech startups’ heterogeneous growth trajectories

Startups are crucial job creators and drivers of economic growth. Research on startups has predominantly targeted high-growth startups, while a comprehensive understanding of alternative growth journeys remains limited. Addressing this gap, we employ the theory of early firm growth and the time-calibrated theory of entrepreneurial action to examine 416 biotech startups. We use time series cluster analysis to unveil four heterogeneous new venture growth trajectories. These are characterized by unique timings, paces, and sequences of financial, human, and innovative resource-related activities. This study contributes to new venture growth research, particularly in science-based high-tech startups, with its nuanced understanding of diverse growth pathways, including intriguing notions of early failure, growth reversal, and high and moderate steady growth.

Approval Delay in Drugs from Non-Global Company in Europe and Japan: Analysis of Novel Drugs for Hematologic Malignancies

Background: Since most therapeutic agents for hematologic malignancies are developed and first approved in the US, it is important for each country to review and approve these agents without delay. Recently, the number of drugs developed by non-global companies including biotech start-ups has increased. Most of these non-global companies are located in the US, and typically do not have offices outside of the US. Thus, it is possible that drugs developed by non-global companies are likely to be approved later in countries other than the US, including the EU. However, their characteristics have not been fully evaluated. Study Design and Methods: Using the public database of the Food and Drug Administration (FDA) from January 2011 to December 2020, new molecular entity (NME) drugs for hematological malignancies that were approved in the US during the relevant period were identified. Cellular products, including chimeric antigen receptor (CAR)-T cells, were excluded from this analysis. NMEs for hematological malignancies were divided into two categories according to the applicant company: NMEs from non-global companies (non-Global group) and NMEs from global companies (Global group). Global companies were defined as those with branches or headquarters in all following regions: the US, the EU, and Japan. The others were classified as non-global companies. Based on the public databases of Japanese regulatory agency (PMDA) and European regulatory agency (EMA), we estimated the rate at which these drugs remained unapproved (unapproved rate) using the Kaplan-Meier method. The unapproved rate of NMEs was compared between the non-Global and Global groups. Results: A total of 39 NMEs for hematologic malignancies approved in the US during the study period were identified. Of these, 13 (33%) NMEs were from non-global companies (non-Global group) and 26 (67%) NMEs were from global companies (Global group). The proportion of orphan drug (13/13 vs. 26/26, p=1.000) and priority review designation (12/13 [92%] vs. 22/26 [85%], p=0.648) were not significantly different between the non-Global and Global groups. In the non-Global group, 12 (92%) NMEs were from the companies headquartered in the US, while 10 (39%) NMEs were from the US companies in the Global group. The proportion of pivotal phase Ⅰ/Ⅱ trial used for marketing authorization in the US was significantly higher in the non-Global group (11/13 [85%] vs. 13/26 [50%], p=0.045). The proportion of pivotal trials enrolling Japanese participants was lower in the non-Global group (0/13) than in the Global group (6/26 [23%]), while the proportion was similar in the EU (9/13 [69%] in the non-Global group and 16/26 [62%] in the Global group). In the EU, the unapproved rate 2 years after the US approval was higher in the non-Global group (54% vs. 22%), but the 5-year unapproved rate was rather lower than that in the Global group (15% vs. 22%) (Figure 1a). Similarly, in Japan, the unapproved rate of NMEs in the non-Global group was higher at 2 years (92% vs. 65%), but rather slightly lower than that in the Global group at 5 years (20% vs. 35%) (Figure 1b). After the US approval, 9 (69%) of the 13 NMEs filed by non-global companies had subsequently partnered with or been acquired by the global companies. Discussion and Conclusion: In both the EU and Japan, drugs in the non-Global group had a higher unapproved rate at 2 years. Notably, 54% of the drugs in the non-Global group were not approved in the EU, even though the participation rate in the pivotal trial used for US approval was similar between the non-Global and Global groups in the EU. However, at 5 years, the unapproved rate had decreased to approximately 20% in both the EU and Japan, presumably due to the fact that lots of the non-global companies were subsequently partnered with or acquired by the global companies.

Financing repurposed drugs for rare diseases: a case study of Unravel Biosciences

BackgroundWe consider two key challenges that early-stage biotechnology firms face in developing a sustainable financing strategy and a sustainable business model: developing a valuation model for drug compounds, and choosing an appropriate operating model and corporate structure. We use the specific example of Unravel Biosciences—a therapeutics platform company that identifies novel drug targets through off-target mechanisms of existing drugs and then develops optimized new molecules—throughout the paper and explore a specific scenario of drug repurposing for rare genetic diseases.ResultsThe first challenge consists of producing a realistic financial valuation of a potential rare disease repurposed drug compound, in this case targeting Rett syndrome. More generally, we develop a framework to value a portfolio of pairwise correlated rare disease compounds in early-stage development and quantify its risk profile. We estimate the probability of a negative return to be 80.8% for a single compound and 56.1% for a portfolio of 8 drugs. The probability of selling the project at a loss decreases from 79.2% (phase 3) for a single compound to 55.4% (phase 3) for the 8-drug portfolio. For the second challenge, we find that the choice of operating model and corporate structure is crucial for early-stage biotech startups and illustrate this point with three concrete examples.ConclusionsRepurposing existing compounds offers important advantages that could help early-stage biotech startups better align their business and financing issues with their scientific and medical objectives, enter a space that is not occupied by large pharmaceutical companies, and accelerate the validation of their drug development platform.

Success factors in drug discovery and development

The article aimed to give a personal perspective on drug discovery and development. The author has worked both in Big Pharma as a scientist and manager and more recently also in start-up biotech companies. Drug companies have played a major important role in improving population health and will continue to do so. The hurdles and costs for drug development have continuously risen without a parallel enhancement of productivity. There is no single explanation for this and the article outlines success factors and hurdles for effective drug development. Aspects of the external and internal environments that influence Big Pharma productivity is outlined and discussed.

[Accelerating drug discovery process with genome editing technology from Tokushima].

In a series of drug development processes from basic research to non-clinical and clinical trials, genome editing technologies have been making innovative breakthroughs. Genome editing using CRISPR/Cas9 system, which was awarded the Novel Prize in Chemistry in 2020, has greatly streamlined the production of genetically modified mice and cells, which have been used in a variety of drug discovery research and non-clinical trials. Setsuro Tech Inc. (Setsurotech) established in 2017 is a biotech startup originated in Tokushima University. In this paper, we will briefly review genome editing technology using CRISPR/Cas9 system, and then introduce our company, our fundamental technologies; GEEP method (Genome Editing by Electroporation of Cas9 Protein) developed by Takemoto et al., and VIKING method (Versatile NHEJ-based Knock-in using Genome Editing) established by Sawatsubashi et al. Also, we will introduce our contribution to the field of drug discovery research and industrial application of genome editing technology.

HPR83 Coming to America: How Ex-US Drug Companies May Best Prepare for the Complexities of a US Market Product Launch

To determine the unique US policy and market access nuances which must be addressed for ex-US biotech companies or startups to enter the US market. The aim of this study is to determine what ex-US biotech startups must understand and focus on within the US market access space to best position new drug launches, given the differences among landscapes. Additionally, this work provides a framework of required issues to explore during early decision-making process in a pre-launch setting.

Medical institutions in the geography of innovation: evidence from public tertiary hospitals and biotech start-ups in Chinese cities

ABSTRACT Concerning China’s growth in biotechnology, the research on biotech start-ups in China yields significant implications. However, studies have not given enough attention to hospitals, which are critical players in the biotech industry. Because of the hospital-centric healthcare system, public tertiary hospitals in China are important partners for biotech start-ups. This study investigates the geographical relationship between public tertiary hospitals and biotech start-ups in Chinese cities. The findings suggest evidence of collocation, which reflects their alliances. This research thereby contributes to the existing knowledge of the biotech industry by integrating the healthcare system into the location of biotech firms.

Complement-targeted therapeutics: An emerging field enabled by academic drug discovery.

Within a short few years, the number of complement inhibitors that are either approved for therapeutic application or evaluated in late-stage clinical trials has expanded remarkably. The sudden emergence of this target area in the pipelines of many biotech start-ups and even large pharmaceutical companies appears even more surprising when considering that the involvement of the complement system in various clinical conditions had long been recognized. In many aspects, however, the complement system is far from being a traditional drug target, which may explain the delayed breakthrough of this therapeutic strategy. While complement modulation is now considered an attractive "platform technology" with applications in a wide spectrum of disorders, the broad yet heterogeneous disease involvement of the complement system has long restricted its placement in traditional drug discovery programs. Concerns about the safety of complement-targeted interventions, the large number and high plasma concentrations of target proteins, and the complexity of the complement system's engagement in biological processes are among other factors that kept complement off the drug discovery radar for decades. Alongside technical advances and financial incentives, the innovation and persistence of academic and clinical researchers have been the critical driving force to navigate complement therapeutics out of the shadow into the spotlight. In this commentary, we document this remarkable development using select examples and aim to venture some predictions where this promising field may be headed to.

WRIB Poster Awards winners 2022

BioanalysisAhead of Print Special FeatureFree AccessWRIB Poster Awards winners 2022Chong Kim, Magali Carcenac, Hua-Chen Chang, William McAuliffe & Moo-jin SuhChong Kim*Author for correspondence: E-mail Address: chong.kim@astrazeneca.comAstraZeneca, Gaithersburg, Maryland, United StatesSearch for more papers by this author, Magali CarcenacSanofi, Montpellier, Occitanie, FranceSearch for more papers by this author, Hua-Chen ChangLabcorp Drug Development, Indianapolis, Indiana, United StatesSearch for more papers by this author, William McAuliffeTakeda Development Center Americas, Cambridge, Massachusetts, United StatesSearch for more papers by this author & Moo-jin SuhAstraZeneca, Gaithersburg, Maryland, United StatesSearch for more papers by this authorPublished Online:24 Mar 2023https://doi.org/10.4155/bio-2023-0048AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: bioanalysisbiomarkerscell therapygene therapyimmunogenicityvaccineWRIBIntroductionThe 16th edition of the Workshop on Recent Issues in Bioanalysis (16th WRIB) was held on 26–30 September. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition.As in previous years, this year's WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.Bioanalysis and Bioanalysis Zone are very proud to continually supporting the WRIB Poster Awards, and we feature the profiles of the authors of the winning posters. Visit www.bioanalysis-zone.com to see the winning posters in full.Development of PK & ADA methods for trispecific antibody: comparison of technologies & optimizationMagali Carcenacmagali.carcenac@sanofi.comPlease can you explain about your role at Sanofi?I am a team leader in the Biological Analysis group within the Biomarkers and Clinical Bioanalysis department at Sanofi, Montpellier (France). Our portfolio presents a large diversity of biological projects that require innovative therapeutic approaches in different indications. Our group develops and validates analytical methods in PK, immunogenicity and biomarker assays in order to assess preclinical and clinical samples in this context.How does it feel to win the 16th WRIB Poster award?I was very proud to win this award and especially grateful to the WRIB team. I was the ambassador for my group and this award is the achievement of the engagement of the whole team which participated in this amazing and thrilling work. We did celebrate this achievement as it should be.Please can you tell us a little about the work on which the Poster was based?The work consisted in developing pharmacokinetic (PK) and anti-drug antibody (ADA) methods for a trispecific antibody, T cell engager, in support of clinical studies.This project was a new challenge due to the expected criteria (sensitivity, selectivity, robustness and target tolerance). We decided to take the risk to evaluate several technologies present in our laboratory, in order to meet the expectations of the project. Three platforms were assessed: SMCxPro, QuickPlex SQ120 and GyrolabxPlore.For Safety reasons and to comply with Health Authorities recommendations, the ADA method has to be highly tolerant to the free drug. Thus, the PEG and Acidification assay (PandA) was selected but must be optimized according to the characteristics of the trispecific antibody.What were the key conclusions from your research?The current results were also based on strong interaction with the clinical teams. Both PK and ADA methods were used to analyze patient samples in the current clinical study. Data recorded confirmed that methods were successfully developed and implemented for patient target population and coped to the analytical challenges to support this clinical study.What are you looking forward to working on over the next year?We look forward to working on therapeutic molecules in rare diseases and addressing complex analytical challenges to improve patients' lives through the miracles of science.Assessment of immunogenicity in SARS-CoV-2 naïve & convalescent subjects following COVID-19 vaccinationHua-Chen Changhua-chen.chang@labcorp.comPlease can you explain about your role at LabCorp?As an Associate Director of Immunology at Biomarker Solution Center in LabCorp Drug Development (a contract research organization), my primary role was to work with clients to provide scientific leadership in translational preclinical/clinical studies, assay qualification and validation, contributing to RFP/RFI documents, and responding to inquiries and providing solutions, which ultimately help clients to navigate the testing laboratories that meet the scope and needs for their studies. My job function was also to leverage emerging technologies and platforms for advancement of biomarkers for drug development. It was a privilege to work with the talented and dedicated colleagues in Covance/LabCorp for 7 years, I recently transitioned to a pharmaceutical company (Loxo@ Lilly) where I will continue the mission to advance drug development for improving human lives.How does it feel to win the 16th WRIB Poster award?I still find it unbelievable that I won the 16th WRIB poster award! It's already a great honor to be accepted for our poster presentation. I must confess that I almost clicked the “phishing” button when I received this award email as I'd never expect to be receiving such an accolade. All the memory of this project came back vividly: from the initial internal grant application to the final legal review of the poster. Across multiple teams globally, everyone worked diligently to ensure that all the assays of this project met the highest standard. The commitment from the LabCorp Science Counsel not only supported the execution of this project, but also set a precedent for more innovative research to come. After realizing that I wasn't dreaming, I immediately forwarded this email to my co-authors and colleagues to spread the joy and glory!Please can you tell us a little about the work on which the Poster was based?Current guidelines from the CDC regarding booster shots for COVID vaccines are largely based on the levels of neutralizing antibody against the spike protein. Despite the indispensable role of T helper cells on the antibody production by B lymphocytes, it's less clear about the level of T cell immunity in determining whether the person is adequately protected from the SARS-CoV-2 viruses. In this poster, we set out to assess the immunogenicity in SARS-CoV-2 naïve and convalescent subjects following COVID vaccination by measuring both humoral and cellular immunity. Enzyme-linked immunospot (ELISpot) assay was utilized for detection of antigen-specific T cells in PBMCs following ex vivo stimulation with different peptide pools (individually or in combination), which encompass the entire spike protein of Wuhan strain of SARS-CoV-2 viruses. In addition to the T cell immunogenicity, serum samples collected from these same donors were analyzed for the levels of neutralizing antibody titers using the PhenoSense® pseudovirus assay. Results allowed us to investigate any correlation between the levels of humoral (neutralizing antibody titers) and cellular (IFNg spot counts) immune responses in the vaccinated subjects who have never been exposed to SARS-CoV-2 viruses (naïve group) and those who have been infected with the viruses (convalescent group).What were the key conclusions from your research?A stronger humoral immune response was found in convalescent subjects after vaccination. However, convalescent subjects with a stronger humoral immune response following vaccination do not always have a robust T-immune response. There is no correlation between the levels of neutralizing antibody and spike-specific T-cell responses in subjects participating in this study. Results provide insights to further understand the spectrum of immunity elicited by COVID vaccines.What are you looking forward to working on over the next year?I'm excited about the precision medicine that promises to advance and revolutionize the treatment of cancer. I'm looking forward to continuing learning the progress of molecular programs (large and small) for targeted cancer therapy. I'd like to explore new tools and approaches to further investigate the drug resistance on a single cell level, and to identify modalities that can overcome such limitations, which could ultimately result in a more efficacious regimen and a better outcome. In addition to research, I'd like to understand the FDA regulations for targeted therapy and companion diagnostics (CDx). Not only for approval of a targeted therapy by the FDA, but also how to utilize the CDx criteria to delineate the underlying biology of tumor burden and cancer types, which can be more informative for effective treatment.Development of a machine learning model for guiding the development of anti-drug antibody assaysChong KimChong.Kim@astrazeneca.comPlease can you explain about your role at AstraZeneca?I serve as an outsourcing specialist and bioanalytical lead at AstraZeneca. I support all phases of drug development – pre-clinical drug discovery and GLP studies, phase 1–3 clinical studies, and regulatory submissions. I specialize in PK and ADA ligand-binding assays.How does it feel to win the 16th WRIB Poster award?It was indeed my greatest honor to win this poster award. This was my first time attending WRIB and I was very impressed by the science and expertise in the bioanalytical community. I am thankful to be part of this wonderful group of scientists and make contributions.Please can you tell us a little about the work on which the Poster was based?Anti-drug antibody assay development is probably one of the most challenging aspects of large molecule bioanalysis. Depending on the assay format and quality of reagents, we often see markedly different assay performance that requires a series of troubleshooting and optimization experiments. In most cases, we rely on our intuition to design the experiments and assay conditions. However, such an approach tends to be time-consuming and inefficient and depends heavily on the experience of the scientist.The goal of our project was to use machine learning to speed up the ADA assay development process. We used a large set of data (∼2500 data points) that we had generated across 34 different method development projects. We initially fed the machine with all the data we had, but it failed to understand what these data points meant. To help the machine understand our data better, we created a new variable called DAC (Detectable ADA Concentration) based on various assay parameters such as master-mix concentrations and MRD. This variable, paired with the Boosted Ensemble of Decision Tree model, showed great potential in predicting ADA assay performance under various conditions.What were the key conclusions from your research?Our model was able to use the input parameters to predict the outcome of each assay condition and predict assay characteristics such as drug tolerance and sensitivity. Such in silico data exploration can help shorten the time-consuming assay ADA assay development.What are you looking forward to working on over the next year?While machine learning is quite popular in the pharmaceutical industry, its use in bioanalysis has been quite limited. In this regard, this project was a great starting point because we saw very promising results using real datasets. The next step is to validate and improve the model. We are working on identifying more sophisticated input parameters (e.g., antibody affinity) to boost the predictive performance of the model. In addition, we are using our new datasets to validate the model. Exciting updates are coming up in the future.Qualification of a Machine Learning Approach for the Analysis of High-Dimension Immune-Profiling Data in Celiac DiseaseWilliam McAuliffeWilliam.McAuliffe@takeda.comPlease can you explain about your role at Takeda?As a scientist at Takeda, I support clinical biomarker strategies in various aspects of drug development and therapeutic areas, specifically through the development of biomarker methods in collaboration with our translational teams. It's an exciting time in drug development with many new modalities and opportunities to make an impact on patient health. And in this field, I can apply my interest in translational work to advancing bioanalytical/biomarker approaches to drug development.How does it feel to win the 16th WRIB Poster award?Honestly, I was surprised at first and now I am very thankful for the opportunity to share this project with the broader bioanalytical community. I suspect there may be many of us in this field challenged with the ever-increasing complexity of datasets derived from our studies. So, I was thrilled to learn this work is of interest to others and can potentially be a useful example more broadly.Please can you tell us a little about the work on which the Poster was based?At times we face challenges with managing the analysis of our high-dimension (i.e., large, and complex multiparameter) datasets derived from our clinical translational efforts.For example, one of the many biomarker platforms we utilize involves a type of single cell cytometry that allows us to identify and resolve the myriad of immune cells that may be present in our clinical trial patient samples more fully. By using this platform, we may gain insight into potential biomarkers of disease state or therapeutic effect.Technically speaking, this platform is an immunophenotyping method called CyTOF which allows us to assess many more cellular identification markers than traditional approaches. But due to the high-dimension nature of the resulting dataset challenges can arise in the analysis of the data.In this poster we give an example of our efforts to assess whether machine learning (ML) can help to explore the full potential of complex datasets such as from CyTOF.We applied ML approaches to CyTOF immune-profiling data from two independent, well-characterized Takeda celiac disease (CeD) clinical studies.By taking this approach of using familiar controlled study data, we were able to ‘qualify’ the ML process to give us more confidence in the results and guide us along the way.What were the key conclusions from your research?This study demonstrated that the FlowSOM machine learning algorithm may be a viable approach to interrogate high-dimension data sets. We were able to qualify this specific ML process and results by confirming known controls in the existing dataset.Machine learning may be used as a complementary approach, secondary to hypothesis driven manual gating, to confirm immune subset findings and to yield deeper cell subset characterization not evident with traditional approaches.What are you looking forward to working on over the next year?I am looking forward to working on progressing some of our programs by potentially applying some of our learnings on ML. For example, We now have an effective ML process example on hand to use for any future high-dimension immune profiling studies. And this is very helpful, because although the poster did not get a chance to illustrate this fully, there was substantial pre-study effort to screen out other non-viable ML approaches that did not work out quite as well for this application, for various reasons.Some interesting immune findings that were derived only from this ML exercise, and not traditional approaches, may be worthy of follow-up in future studies and may help us gain insight into celiac disease.A Novel Hybrid LBA-micro-flow LC–MS/MS assay for PK Bioanalysis of ADCsMoo-Jin Suhmoo-jin.suh@astrazeneca.comMoo-jin Suh is an Associate Director in the Integrated Bioanalysis Group, Clinical Pharmacology and Safety Sciences, at AstraZeneca in Gaithersburg, MA (USA). Moo-jin obtained his PhD degree in Chemistry from the University of Cincinnati (OH, USA) and has 2.5 years of postdoctoral training in pharmacology, at Weill Medical College of Cornell University (NY, USA). Prior to joining AstraZeneca in 2021, Moo-jin built his expertise in proteomics, infectious disease, and antibodies in research and industry sectors (e.g., J Craig Venter Institute, US Army Medical Research Institute of Infectious Disease, and Startup biotech).Moo-jin's expertise lies in high-throughput discovery bioanalysis, mass spectrometry, proteomics, structure elucidation of small molecules, imaging mass spectrometry, characterization of antibodies, and biomarkers in complex biological matrices. Moo-jin has authored more than 28 peer-reviewed publications and book chapters in the areas of Analytical Chemistry, Infectious disease, and Proteomics.Please can you explain about your role at AstraZeneca?As an Associate Director within AstraZeneca's Integrated Bioanalysis group, I am responsible for setting up the bioanalytical strategy and for developing and optimizing assays for the pharmacokinetic, pharmacodynamic (PD), and biotransformation studies of biotherapeutics to support drug program transition through lead selection and into clinical trials. I work closely with my team and other staff within AstraZeneca for PK/PD studies for biotherapeutics (T cell engager, and antibody-drug conjugate) and for exploring potential relationships with safety and efficacy.How does it feel to win the 16th WRIB Poster award?It was an honor to be selected as a recipient of the 16th WRIB poster award. When I heard that I had been awarded, I was quick to inform those who made this possible (Josh Powers, Casey Daniels, Yuling Wu) and we were all thrilled to receive this prestigious award. I feel honored to have our work be selected and can't wait to use the feedback I got in order to better my work in the future. I would like to thank you all for giving me this opportunity, thinking of it as an encouragement to work harder.Please can you tell us a little about the work on which the Poster was based?It has been an outstanding decade for the field of antibody drug conjugates (ADCs), with the approval of more than 8 new ADCs. With the ongoing evolution of ADCs portfolio utilizing site-specific conjugation and a small amount of highly cytotoxic payload, and administering a lower dose of ADCs, more sensitive bioanalytical platforms are highly desirable for quantifying major analytes of ADCs to comprehensively understand PK behavior of ADCs in vivo. The goal of this study was to demonstrate the feasibility of a hybrid ligand-binding assay/microflow liquid chromatography-tandem mass spectrometry (LBA/μLC–MS/MS) for use in the PK study when sample quantities are precious. After optimization, the total antibody PK data from a hybrid LBA/μLC–MS/MS was compared with that of ELISA acquired from the same samples, demonstrating feasibility of a hybrid LBA/μLC–MS/MS. Furthermore, we demonstrated multiple and diverse analytical assays (total antibody, intact antibody and total ADC) with the hybrid LBA/μLC–MS/MS in the challenges of ADC bioanalysis.What were the key conclusions from your research?Sample preparation is one of the most important steps to achieve good results in bioanalysis. For sensitive instruments such as μLC–MS/MS, appropriate sample preparation methods (Immunoaffinity capture, efficient digestion, solid phase extraction, etc.) suitable for μLC–MS/MS were selected for downstream analysis. The use of a highly sensitive hybrid LBA/μLC–MS/MS in the current study was reported for quantification of total antibody, intact antibody and total ADC in sub-microliter sample volume. Together with ELISA approach, this method provides another powerful and sensitive analytical platform for understanding the fate of ADCs in vivo.What are you looking forward to working on over the next year?It is predicted that the use of a hybrid LBA/μLC–MS/MS will gradually increase in order to obtain comprehensive PK information in biotherapeutic dosed samples. In particular, measuring trace amounts of free payload present in circulation provides important information for toxicity assessment and safety concerns. Furthermore, it is expected that the hybrid LBA/μLC–MS/MS will be readily adopted for experiments requiring high sensitivity (e.g., tumor tissue with limited sample size) and limited samples. The hybrid LBA/μLC–MS/MS can reduce reagent consumption, minimize the use of sample volume, and be suitable for capillary micro-sampling to collect small amounts of biological samples. Therefore, it is anticipated that it may be possible to implement the hybrid LBA/μLC–MS/MS in preclinical PK studies to reduce overall animal use and improve animal welfare.DisclaimerThe opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Newlands Press Ltd.Financial & competing interests disclosureThe interviewees have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.FiguresReferencesRelatedDetails Ahead of Print Follow us on social media for the latest updates Metrics History Received 15 March 2023 Accepted 15 March 2023 Published online 24 March 2023 Information© 2023 Newlands PressKeywordsbioanalysisbiomarkerscell therapygene therapyimmunogenicityvaccineWRIBDisclaimerThe opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Newlands Press Ltd.Financial & competing interests disclosureThe interviewees have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Global or local: The future of biotech

Biotech start-ups often begin as domestic companies relying on local resources and talent, but this approach might not be effective in achieving rapid growth and long-term success, particularly for developing new therapeutics that require significant resources and extensive commitment. Here, we argue that born-global biotechs are better equipped to tackle major industry challenges, such as innovation, resource constraints, and limited talent diversity, especially in current challenging times. We also highlight the importance of capital efficiency in maximizing the benefits of being a born-global biotech, and provide an operational framework, based on the FlyWheel concept, for becoming a successful born-global biotech.

Studying the governmental, industrial, and academic partnerships between incubation centers for furthering innovation: Evidence from biotechnology firms in Singapore

In Singapore, the number of incubation centers is rapidly increasing to fulfill the demands of the associated audience. These centers are vital in providing important facilities and capitals for new start-ups. This study aimed at identifying the governmental, industrial, and academic partnerships between incubation centers for furthering innovation in biotechnology firms in Singapore. For this purpose, semi-structured interviews were conducted with five employers from top management in biotechnology firms in Singapore. After the collection data, qualitative analysis was conducted in two steps (step 1: thematic analysis and step 2: word cloud analysis). The results obtained from this study showed that incubation centers play an important role in establishing early-stage biotech start-ups, promoting bio-entrepreneurship. It has also been observed that different challenges are faced during incubation process which include legal issues, infrastructure issues, strategic alliances issues and others. Moreover, the governmental, industrial, and academic partnerships between incubation centers have proven to be effective in promoting innovation processes in biotechnology firms.

How to Develop a Rare Disease Treatment

GEN BiotechnologyVol. 2, No. 1 Book ReviewsFree AccessHow to Develop a Rare Disease TreatmentSean EkinsSean Ekins*Address correspondence to: Sean Ekins, Collaborations Pharmaceuticals, 840 Main Campus Drive, Lab 3510, Raleigh, NC 27606, USA, E-mail Address: sean@collaborationspharma.comCollaborations Pharmaceuticals, Raleigh, North Carolina, USA.Search for more papers by this authorPublished Online:15 Feb 2023https://doi.org/10.1089/genbio.2023.29075.sekAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Saving Ryan: The 30-Year Journey into Saving the Life of a Childby Emil D. Kakkis (Impositivity Media, LLC, 2022).There are several excellent books about patients diagnosed with a rare disease [e.g., Gina Kolata's Mercies in Disguise (St Martins Press, 2017)] or about building a rare disease biotech, such as A Rare Breed by Daniel Levine and Daniel Maher (Biomarin, 2017) and Conscience and Courage by John Hawkins (Cold Spring Harbor Laboratory Press, 2019). Published in 2022, Saving Ryan by physician/scientist and entrepreneur Emil Kakkis successfully merges the story of a rare disease patient chasing a life-saving treatment with the clinician scientist's perspective of developing it.(My company has benefitted from Emil's generosity in providing a letter of support for a rare disease grant.) The author's compassion and willingness to help others who are developing rare disease treatments shine in every page. He even started a publishing company to self-publish the book to provide a story of hope.Inspiration and FrustrationThe book blends autobiography, inspirational read, and instructions on how to make an enzyme replacement therapy (ERT) for a rare disease. Kakkis tells the story of Ryan Dant, who was diagnosed as a young child with a lysosomal storage disease, mucopolysaccharidoses type I (MPS I). His parents are determined to fund a treatment to save his life.MPS I is caused by a mutation in an enzyme iduronidase, which clears glycosaminoglycans. In patients lacking this enzyme, these build up in the joints and various organs and may lead to life-threatening complications. Emil and the Dants cross paths in 1995, raising significant funds that helps Emil and his laboratory develop the treatment. A start-up biotech (Biomarin) and then a bigger biotech (Genzyme) provide additional funding and expertise, resulting in clinical trials and ultimately, in 2003, approval by the FDA.That is the abbreviated story. What is remarkable is the “warts and all” telling of it, especially the numerous hurdles that must be surmounted and unexpected setbacks that reminded me of a game of snakes and ladders. We hear a perspective from a clinician/principal investigator in an academic laboratory who must balance the ups and downs of hiring staff, the challenges of raising funds, and ultimately the dual pressures of publishing vs continuing research to develop a treatment.Kakkis spares no details in the ups and downs of working with the FDA. Over 2 years, the relationship went from very supportive to delaying the treatment reaching the market, necessitating an additional clinical trial and millions of dollars of further investment to be raised. Kakkis surprisingly names those people at the FDA, whom he alleges cost several children's lives by delaying treatment availability. Working on such rare diseases is heartbreaking and Kakkis took those losses personally.In the epilogue, Kakkis provides an update on the participants in the first clinical trial. Sadly, 6 of the 10 are no longer alive, likely because they were treated relatively late, and the effects of the disease were already advanced. The remaining four are living productive independent lives, which previously would have been unimaginable.TranslationAs someone developing an ERT for a rare disease (Batten disease), the timing of this book could not have been better. We learn every step in the process of how an ERT is made and tested before translation to the clinic. The book is a well-written “how to” manual. Not that everyone will be able to follow in his footsteps, but Kakkis provides a roadmap for other families and scientists.An index would have added to the book's value. The scientific explanations of lysosomal diseases are clear and the author pays tribute to the pioneers such as Elizabeth Neufeld working on rare genetic diseases who discovered the mutation that causes MPS I and laid the foundation for eventual treatments. Kakkis started working on MPS I not in some swanky modern laboratory but in a bungalow laboratory from the 1940s at Harbor-UCLA Medical Center in Torrance, CA, which ultimately had to be retrofitted to be able to provide Good manufacturing practice conditions to make clinical material.The detailing of the “shoestring science” and agonizing efforts to make tiny quantities of enzyme for the initial preclinical studies in dogs is revealing for how little it cost to get this far in 1993, likely tens of thousands of dollars and many very long days. Kakkis made it work with part-time staff and second-hand equipment, but he was clearly very demanding.As Kakkis raises more money, the team grows and so does the protein production scale. You get the sense that if more academics were like him and not continually chasing publications, grant funding, and tenure, we would have more treatments available for patients. Kakkis ultimately sacrificed his academic career to bring hope to the families of MPS I patients, but his route in biotech also positioned him well to become an entrepreneur, starting his own company.ImpactThe monumental effort to get the ERT treatment approved ultimately led to the product Aldurazyme being used by >1000 people around the world, leading to newborn screening for the disease. Kakkis intertwines this story with the more personal story of the Dants' fundraising efforts and their hopes and fears for their son. There is a happy ending for Ryan and plentiful photos to chart his life from young child through to married adult. Kakkis has been at Ryan's side for many of his milestones. He spent 11 years at Biomarin bringing six more treatments to market (which he mentions in passing), rising to chief medical officer. He then started a foundation to work with the FDA, congress, and companies to help improve the process of bringing treatments to patients.In 2010, Kakkis founded Ultragenyx to work on rare and ultrarare diseases, developing an ERT for MPS VII, for which the FDA provided compassionate access. Perhaps more importantly, Kakkis serves as an inspiration for families, and he provides much useful advice throughout this book. For example, The Ryan Foundation had a massive impact on his laboratory and ability to develop the ERT, something other families should heed. They could focus their funds and resources on supporting young scientists without NIH funding.Some diseases will be tough to address with ERTs, but Emil makes a strong case for their potential (at the outset he wanted to work on gene therapies but was nudged toward ERT). Kakkis' biggest impact may be to inspire the hundreds if not thousands of other families and scientists who are also looking for a cure or a purpose, respectively.Providing HopeSaving Ryan is an important historical document. Will we look back on the early 2000s as a turning point with companies including Biomarin and Genzyme developing ERTs? Like many other companies, they have also invested heavily in gene therapy, with no treatments to show for it. What have we lost by not continuing to develop the technologies for producing more ERTs that might also enable them to be made more cost-effectively?I would have liked Kakkis to talk more about the future, what technologies could be used to enable developing ERTs to scale. Nevertheless, Kakkis has shown what is possible and perhaps others will pick up the baton. Saving Ryan shines a light on how a family foundation can have a dramatic effect on funding cutting-edge science. The next time you are asked to sponsor someone or participate in a charity golf tournament for a rare disease, remember that your generosity could help the next breakthrough therapy, leading to a story of hope that will one day be told just like this one.FiguresReferencesRelatedDetails Volume 2Issue 1Feb 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:Sean Ekins.How to Develop a Rare Disease Treatment.GEN Biotechnology.Feb 2023.27-28.http://doi.org/10.1089/genbio.2023.29075.sekPublished in Volume: 2 Issue 1: February 15, 2023PDF download

Patient Advocacy Leads to Synthetic Antibodies for Mycobacteria

GEN BiotechnologyVol. 2, No. 1 CommentaryFree AccessPatient Advocacy Leads to Synthetic Antibodies for MycobacteriaMonica Berrondo and Varun ThvarMonica Berrondo*Address correspondence to: Monica Berrondo, CEO, Macromoltek, 2500 W William Cannon Dr Suite 204, Austin, TX 78745, USA, E-mail Address: monica@macromoltek.comCEO, Macromoltek, Austin, Texas, USA.Search for more papers by this author and Varun ThvarIntern, Macromoltek, Austin, Texas, USA.Search for more papers by this authorPublished Online:15 Feb 2023https://doi.org/10.1089/genbio.2023.29080.mbeAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail A small biotech company is applying a novel computational approach to design antibodies to tackle antibiotic-resistant bacterial infections.Rarely do small biotech companies pursue projects instigated by patients themselves. But patient advocacy groups in the rare disease space aim to change that. These groups are led by patients who are anxious to cure their own disease or their friends and family who are eager to help others handle the struggles of a new or rare disease. In late 2018, I was connected serendipitously to one such family.I met junior high school student, Varun Thvar, in the Fall of 2018 while raising money in the San Francisco Bay Area for my small company, Macromoltek. I started the company several years earlier with the dream of personalized medicine and a lofty goal to cure any disease at the push of a button, relying on the power of computational biology.Varun's mother had developed a very rare infection caused by the bacteria, Mycobacterium abscessus (MABC). His mother's infection had sparked Varun to learn more about the drug discovery process in general, and drug discovery for the MABC infection in particular. The family had set up a small foundation to find a cure for the disease and learned about our accelerated process of drug discovery. Varun had been inspired by the bacille Calmette-Guérin vaccine for tuberculosis and the use of antibodies instead of antibiotics in the treatment of infectious disease, but learned that MABC did not yet have any antibody-based treatments available. When Varun contacted me, I was intrigued by the problem as well as the use of the project as a case study for Macromoltek's technology. As a result, it became clear that designing an antibody for MABC could validate our capabilities while also tackling other important pathogens.Varun's mother had to endure an exhausting and excruciating process for both diagnosis and treatment. The initial presentation was a sudden onset of a 104°F fever. As the family learned, diagnosis of the MABC infection was a circuitous process that required ruling out various other causes before a bronchoscopy eventually led to an MABC diagnosis. Her treatment consisted of a harsh combination of antibiotics.After an initial positive response to the treatment, the MABC infection developed immunity to the antibiotic combination within just 4 weeks. A second bronchoscopy was performed to ascertain which remaining antibiotics could be effective against the MABC strain. Unfortunately, the results showed that very few treatment options remained—the MABC infection had become highly drug resistant. Consequently, the treatment cocktail method of delivery was updated and all antibiotics were delivered intravenously through a peripherally inserted central catheter line in a twice-daily regimen of 2–3 hours each time. This course of treatment continued for the next 9 months, after which a lung resection was used to remove the affected area. Fortunately, after a 12-month ordeal, Varun's mother recovered and became the inspiration for Varun to reduce the suffering of others through drug discovery.MABC DefinedMABC is a rapidly growing bacteria that is responsible for a number of severe pulmonary infections, especially in patients with chronic lung disease. MABC infections are characterized by a resistance to antibiotic treatments and comorbidities with other respiratory illnesses. As a result, these infections are a serious concern, similar to what we have seen with other respiratory infections, such as COVID-19.An analysis of 107 patients between 2001 and 2008 identified that patients with MABC infections were predominantly female, nonsmokers, and with an average age of 60 years.1 MABC infections are found in both patients with and without existing respiratory conditions, such as lung airway abnormalities. Although environmental reservoirs of MABC have not been confirmed, the bacteria have been found in biofilms in many sources, including shower heads. Insufficient evidence has been collected to suggest changes in patient behavior could aid in preventing MABC infections.The increasing profile of MABC infections is due to the infection's uniquely strong antibiotic resistance. Although some patients receive surgical treatment, the MABC infection is too extensive for effective surgical resection for most patients. For other patients, multidrug cocktails, including clarithromycin, are a standard treatment, but the clinical efficacy of such approaches varies on a case-by-case basis.As in this example, treating MABC infections requires huge resources and effort for each patient. As the treatment is not scalable, it is fortunate that MABC infections are not contagious or frequent. However, as we have seen with COVID, a single mutation or variant could increase transmissibility, potentially creating an epidemic of dire proportions.Furthermore, MABC's increased antibiotic resistance and ability to acquire immunity to antibiotics, sometimes over the course of weeks, make it part of the challenging trend of “superbugs” that can defy traditional treatments. Additional treatment avenues, such as phage therapy, have been explored to address MABC. However, obstacles remain in scalability as the strategy is not a “one-size-fits-all.”2Despite the challenges, the pursuit of alternative treatments for MABC might also lead to new insights into cures for other more prevalent diseases such as tuberculosis, which is increasingly becoming antibiotic resistant and is dormant in about a third of humanity.3Process and DiscoveryAfter learning about this disease and meeting Varun, we worked together to develop an antibody against MABC. We invited Varun to visit our company and spend the summer driving the project (Fig. 1). Varun joined our team as an intern, not only to provide insight into the specific needs of those affected by MABC, but also to actively contribute to the project through his own research and analysis. This experience not only allowed us to gain a deeper understanding of the disease and potential treatment options, but also greatly impacted Varun, as he was able to work firsthand on the entire process of designing an antibody from scratch and improving the efficacy in the quest for a cure.FIG. 1. Varun testing antibodies in the Enzyme-Linked Immunosorbent Assay test in the Macromoltek laboratory.At Macromoltek, we use computational biology to design antibodies. Antibody drugs play a critical role in infectious diseases, cancer, autoimmune diseases, and inflammation. However, experimental methods for the generation of therapeutic antibodies, such as using immunized mice or phage display are time-consuming and cannot always be targeted to a specific antigen epitope. In both cases, the process is akin to searching for a needle in a haystack versus tailoring the antibody to the problem of interest. The design of an antibody against a unique epitope on the surface of a protein is an important application of computational methods for antibody design.4–6Toward this end, we have devised algorithms for computational library creation and selection. As we computationally search the space around a particular epitope, we can design antibodies to bind only to that epitope without the need to produce millions of antibodies in the laboratory. This search leads to a small number of antibodies for further experimental testing. Our algorithms combine structural biology and machine learning techniques to reduce the search space to something tractable and epitope-directed.As a small biotech company, we rely on collaborations with academic institutions or large pharmaceutical companies to give us targets to design around or against. These targets are often of high value and priority to pharmaceutical companies because they affect a large number of people. Without dedicated personnel for different diseases, we are caught with the dilemma of either focusing our discovery platform on a single disease or working on projects that outside parties bring us.There are multiple benefits to antibody treatments compared with antibiotic treatments.7,8 First, antibodies are more effective than antibiotics due to the larger surface area and stronger binding to the pathogen. Second, antibody treatments also deliver immunity from future infections, as they can stay in the bloodstream without harming other cells. Third, antibody treatments have fewer side effects than antibiotics and do not negatively impact other organs, such as the liver or kidneys, due to their ability to be tailored to specific pathogens and bacteria, an ability that antibiotics lack.To create functional antibodies targeting MABC, we designed antibodies using computational methods to find potential candidates. After identifying a target protein and creating a computational model, we used deep learning algorithms to generate a map of possible epitopes on the protein surface. For each potential epitope, we used structure-based methods to search the sequence and conformational space on several antibody scaffolds to generate paratopes that matched the selected epitope. This process generated tens of thousands of sequence/structure pairs that were refined and optimized to ensure the final antibody sequences can easily be made in the laboratory and have biophysical properties to make them into a drug. The library of antibodies and their structures were then subjected to a second deep learning model to select the antibodies with the best epitope/paratope match for experimental validation in efficacy and specificity.In comparison with the traditional trial and error method of antibody discovery that can take up to 2 years to yield a hit, this entire process was done over the course of a summer and resulted in two strong candidates. With traditional methods, tens of thousands to millions of antibodies would need to be filtered in the laboratory. This same amount of antibodies were “tested” computationally in a more efficient manner. This method of designing custom antibodies provides a blueprint of possible treatment vectors for various diseases that could help cure more prevalent diseases, such as tuberculosis, COVID-19, and potentially cancer.Looking back at the beginnings of this project, we started with the goal of preventing individuals diagnosed with the MABC infection from experiencing the tortuous treatment process that Varun's mother endured. To this end, we have made initial process developing antibody hits against a protein that is crucial to the life cycle of the disease. The next step is for these resulting antibodies to be tested in vivo to show efficacy and move into clinical trials. Only then can such an approach be implemented into the existing treatment structure. Varun's journey with our company has been a powerful reminder of the importance of patient advocacy and the potential for biotech start-ups to make a meaningful impact in the fight against rare diseases. The dedication and perseverance of individuals such as Varun can inspire others and drive innovation in the field of medicine.

How does disruptive innovation influence the funding decisions of different venture capital investors? An empirical analysis on the role of startups' communication

Entrepreneurs present their ideas in a favorable light through compelling communications that may shape the investors' impressions about the value of the startup's technology and its potential to disrupt. Assessing such communications, venture capital (VC) investors get an impression of the startup's technology and shape their willingness to commit resources to it. Since diverse kinds of VC investors pursue alternative investment objectives, they may develop different impressions of the startup's technology and accordingly make different resource commitment decisions. This paper aims to investigate the resource commitment decisions of VC investors when financing startups communicating disruptiveness by distinguishing between independent venture capitalists (IVC) and corporate venture capitalists (CVC). Analyzing data about 664 medical device and biotech startups in a 10-year period, we found that communicating disruptiveness decreases the amount of funding committed by IVC, while it has a curvilinear effect on the amount of funding provided by CVC. Our findings contribute to the literature and provide important implications for managers of startups aiming to secure funding from different VC investors.

Increasing the success potential of promising biotech companies

Biotech startups benefit society by solving unmet scientific and medical needs, but more can be done to move their technologies to market more quickly.

Deregulating Innovation Capital: The Effects of the JOBS Act on Biotech Startups

Abstract We examine real outcomes for biotech startups going public around the Jumpstart Our Business Startups (JOBS) Act. Reduced compliance costs associate with greater innovation capital formation as biotech IPO volume and proceeds increase after the JOBS Act. Biotechs, which conduct over 30% of IPOs since 2012, go public with products earlier in the FDA approval process and more frequently target rare diseases and cancer. Consistent with our survey evidence that managers use compliance savings to invest in R&D, we link the JOBS Act to post-IPO increases in project-level development, such as new patents, clinical trials, and staffing of laboratories. Post-JOBS Act product candidates are more likely to reach key milestones in the FDA approval process and these startups fail at lower rates. Benefits accrue to shareholders without sacrificing financial reporting quality. Our results demonstrate how tailoring regulations for startups can provide economic and societal benefits. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.

Cell & gene therapy orchestration: supply chain management in real-time

With more Cell & Gene Therapies (CGT) entering the market, many pharma companies are currently looking into their supply chains and adapting them for the complexities and requirements that come with these novel therapies. Many startup biotech companies are doing the same thing, but with the advantage of being able to start with a greenfield project. The complex, highly collaborative supply chains of CGT require control and visibility to fulfill the very high requirements for safety, resilience, and speed that come with the underlying drug products. A very high degree of process complexity and the involvement of many different contributors, each with numerous intermediates and handovers, combine to ensure that it is almost impossible to manage more than 50 patients per year with simple tools such as Excel spreadsheets and web portals. There is a ‘magic tool’ that can provide the necessary support here – one that has been talked about for several years now: the Cell & Gene Therapy Orchestration Platform (Orchestration Platform). Biotech companies may require Orchestration Platform features that support regulatory requirements, such as chain of identity and custody, logistics management, and general collaboration. But as they move with their assets through preclinical, clinical, and eventually, commercial, it becomes clear that each of these different phases come with added requirements for the Orchestration Platform. Step by step, they will require features on different levels (workflow and integration, manufacturing, operations, tactical and strategic), depending on the product lifecycle and organizational state. In this article, we will detail all levels of a complete end-to-end supply chain management approach for personalized therapies. We will also highlight critical features of and key considerations for an Orchestration Platform and describe the phase in the product lifecycle in which each single level begins to generate its full value. 

Biotech’s New York groove

“Two reasons,” says Anthony Johnson, founder and CEO of the biotech start-up Kodikaz Therapeutic Solutions about the decision to launch his company at an incubator in Lower Manhattan. “We knew we wanted to set up in New York City because of the burgeoning biotech scene and all of the infrastructure in place for biotech to be a success,” he says. “Also, we were the inaugural Golden Ticket winner.” That Golden Ticket was issued in 2020 by BioLabs at NYU Langone, the incubator offering Kodikaz free rent for a year. The award was sponsored by the big drug firm Boehringer Ingelheim. With technology from Emory University, Kodikaz is working on a system for delivering cell and gene therapy with DNA fragments. Called Zip-Code, the platform enables targeted delivery of a wider variety of payloads than can be achieved using viruses and other standard delivery methods, the firm says. Kodikaz—the name derives

Moo-re Gene-edited Animals Get Regulatory Clearance: U.S. FDA Approves Genetically Engineered Cattle for Human Consumption

Biotechnology Law ReportVol. 41, No. 3 News BriefsFree AccessMoo-re Gene-edited Animals Get Regulatory Clearance: U.S. FDA Approves Genetically Engineered Cattle for Human ConsumptionBy Steven J. ZweigBy Steven J. ZweigSteven J. Zweig is the Managing Editor of Biotechnology Law Report.Search for more papers by this authorPublished Online:15 Jun 2022https://doi.org/10.1089/blr.2022.29269.sjzAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail United States regulators recently approved Recombinetics' genetically engineered cattle for human consumption, joining gene-modified pigs and salmon as the third engineered animal approved in the United States. Recombinetics used CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to modify the cattle to have short, slick coats better suited to hot weather. The idea is that cattle who are not (metaphorically) wilting in the heat will be able to bulk up more easily, improving meat production. The notion certainly seems to make sense to anyone who's sweated their way through a torpid summer: humans, at least, seem to pack on the pounds more easily during cool weather and it's logical that cattle would too.The review of Recombinetics' cattle was shorter (several months, rather than years) than the reviews of the modified pigs and salmon because their genetic make-up is very similar to that of other cattle, to the extent that the gene-edited trait is already found naturally in other breeds. Dr. Steven Solomon, director of Food and Drug Administration's (FDA) Center for Veterinary Medicine, opined that Recombinetics' approach—building on a trait already found naturally in the subject animals—“opens up a completely different pathway” for approval as opposed to adding a trait not present in the animals' population. As such, he offered that FDA's decision in this case may encourage smaller or start-up biotech companies to follow Recombinetics' example.Even with the shorter review, it's expected to be another two years, perhaps more, before Recombinetics' beef reaches the market.The previously approved genetically modified pigs are intended for medical purposes (e.g., organ transplant) rather than the breakfast or dinner table. The previously approved salmon are for human consumption and are sold to distributors in some regions (e.g., the Midwest and Northeast).New Technology, Same Old ScamInvestment scams—convincing people to invest in vapor while the scam's organizer pockets their investment—are undoubtedly as old as money: almost certainly, there were Mesopotamians who invested their hard-earned shekels in pottery-making or reed boat-building opportunities that never materialized. The advance of technology doesn't change human nature: there will always be fraudsters and scam artists and the desperate, gullible, and overly trusting on whom they prey; all new technology does is give the criminals new dreams to sell.Case in point: Ariel Quiros, former owner of Vermont ski resorts Jay Peak and Burke Mountain, was just sentenced to five years in prison for defrauding 170 investors out of at least US$500,000 each (some considerably more), raising a total of US$400 million through this and related schemes. Sentenced with him were two associates, William Stenger, former president of Jay Peak, and William Kelly, an advisor to Quiros, to 18 months in prison each. A fourth conspirator, a South Korean businessman, presently remains at large.The scam? Quiros and his conspirators convinced foreigners to invest in building the “claimed” AnC Bio biotechnology plant in an economically depressed part of Vermont near the Canadian border. The investors put in their money pursuant to a visa program under which foreigners invest in job-creating ventures in exchange for the opportunity to obtain permanent U.S. residency. Unfortunately, there was no job creation, just as there was no AnC Bio plant being built; as U.S District Judge Geoffrey Crawford said at the sentencing hearing,1 “[t]his project was a fiction from beginning to end.” Quiros pocketed over US$30 million from his victims but ended up coming out well behind: in addition to prison time, he also settled civil charges brought by the Securities Exchange Commission by surrendering US$80 million in assets, including his two ski resorts.Also in Biotech-Related Crime News … Dr. Ishtiaq Ali Saaem, the director of advanced research at Massachusetts biotechnology firm Gen9,2 was sentenced to six months home confinement and a further two-and-a-half year probation for obstruction of justice in conjunction with hindering an investigation with his efforts to obtain ricin, a deadly toxin made from castor beans. Ricin is perhaps most famously (or infamously) known for its use in the 1978 broad daylight assassination of Bulgarian dissident Georgi Markov, killed on a London street using a Bond-movie-worthy device: a contact “umbrella gun” which used compressed gas to shoot a tiny pellet containing ricin into his leg. A passer-by3 “accidently” poked Markov with an umbrella and a few days later, he was dead. Ricin has also been used in other attempted assassinations and terror attacks.Saaem, however, did not take his cue from real-life uses of ricin as a murder or terror weapon, but from the popular television series Breaking Bad, on which it was also used.4 He ordered 100 packets of castor beans, each packet containing eight seeds, and lied to federal law enforcement about it, claiming that he had meant to buy only one packet but “accidently” ordered 100. He claimed he wanted them for gardening—this despite his researching tasteless poisons that could be made at home. He also tried to deny or downplay his knowledge of ricin.It's not Always about Covid: Geovax LABS Receives U.S. Patent Relating to a Malaria VaccineMalaria, a mosquito-borne disease caused by a microscopic parasite, causes almost a quarter-billion infections and over 400,000 deaths per year. It also can cause debilitating complications, including cognitive and neurological deficits, and can reappear or recur in its victims months or years after the initial infection. Because the parasite (members of the Plasmodium group) has a complex, multi-stage lifecycle, it has been difficult to effectively vaccinate against it: historically, most vaccines only target one stage of the parasite's lifecycle.However, GeoVax's in-development malaria vaccine candidates use a Modified Vaccinia Ankara (MVA) virus which has been engineered to express antigens derived from multiple stages of the parasite's lifecycle. By using antigens from several lifecycle stages, it is hoped that the vaccine will induce broader protection than vaccines just targeting one or two stages. While GeoVax is also, in common with just about every pharma and biotech company out there it seems, working on a COVID-19 vaccine, its CEO and president, David Dodd, said that “developing vaccines against global public health threats is also part of our longer-term focus” and that the company's goals “include developing such vaccines that are affordable, highly effective, safe, and [which] can be distributed and administ[ered] across various regions of the world in a simple manner.”Malaria is most prevalent in some of the most impoverished countries in the world and is not merely thought to be a hazard of poverty (e.g., a lack of public sanitation and health resources) but also a cause of poverty. Some studies, for example, suggest that widespread malaria can reduce a nation's annual Gross Domestic Product (GDP) growth to only around a fifth of what it would be without malaria.5 An effective, affordable, easily administered malaria vaccine would be a huge boon.Mission: Impossible BurgerImpossible Foods is the creator of the Impossible Burger. The Impossible Burger and other Impossible Foods meat-substitute or meat-analogue products make it a huge presence in the plant-based protein and meat-substitute market.6 The “secret” to its meat analogues is the use of heme, a hemoglobin precursor, which plays an important role in meat's taste, smell, and texture. Impossible Foods developed a technology using genetically modified yeast to express soy leghemoglobin, which is identical or nearly so to the heme molecule in animals. Its patent on this technology is the crown jewel of the company's intellectual property portfolio.Along comes competitor Motif Foodworks, which uses bovine myoglobin as its heme source. While significantly smaller than Impossible Foods, Motif Foodworks is potentially a formidable competitor: as a 2021 Ginkgo Bioworks spinoff, it already has a valuation of over US$1 billion and has raised around $340 million from investors, including Bill Gates. Impossible Foods brought a patent infringement suit against Motif Foodowrks, claiming that its patent also covers certain beef-substitutes using a muscle replica or fat tissue replicas, such as Motif Foodworks technology uses. Motif Foodworks, in turn, filed a petition with the United States Patent and Trademark Office's (USPTO) Patent Trial and Appeal Board seeking to invalidate Impossible Foods' patent. If Motif Foodowork's challenge to Impossible Food's patent is successful, it will likely lead to increased competition in the meat substitute market.1 There was no trial: Quiros pled guilty in August 2020 to conspiracy to commit wire fraud, money laundering, and concealment of material information, in exchange for other charges being dropped and a favorable sentencing recommendation—Quiros could have received more than five years in prison if convicted at trial.2 Gen9 is now part of Ginkgo Bioworks.3 Believed to be a member of the Bulgarian secret police, though high-level Russian defectors later confirmed that it was the KGB—Vladimir Putin's former outfit—who supplied the ricin.4 Saaem was not the only one inspired by Breaking Bad: several people have been convicted over the years for unsuccessful attempts to commit murder using ricin after the toxin's use on Breaking Bad.5 See, e.g. Sachs J, Malaney P, ”The economic and social burden of malaria”, Nature, 415 (6872): 680–85. doi:10.1038/415680a. PMID 11832956 (2002).6 Impossible Foods and Beyond Meat are the two most-widely known players in this space.FiguresReferencesRelatedDetails Volume 41Issue 3Jun 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:By Steven J. Zweig.Moo-re Gene-edited Animals Get Regulatory Clearance: U.S. FDA Approves Genetically Engineered Cattle for Human Consumption.Biotechnology Law Report.Jun 2022.119-121.http://doi.org/10.1089/blr.2022.29269.sjzPublished in Volume: 41 Issue 3: June 15, 2022Online Ahead of Print:June 6, 2022PDF download