Funding Source Research Articles

Study on Venture Capital Investments and its ability to stimulate Innovation and spur Economic Growth in India

Objective: This paper examines the impact of Venture Capital Investments (VCI) on Innovation and Economic Growth in India. Venture Capital has emerged as a critical source of funding for startups, enabling them to develop innovative ideas, scale their operations, and contribute to economic growth. India, with its vibrant entrepreneurial ecosystem, has witnessed a significant increase in venture capital investments over the past decade. Research Design and Methods used: This paper gathers key information from the market, varying from various reports and relevant data published by private players like E&Y, Bain & Company, Hurun, Venture Intelligence, Indian Venture Capital Association (IVCA); besides,  governmental reports of SIDBI, SEBI, Economic Surveys, MSME Annual Reports and ‘Intellectual Property India’ report published by the Controller General of Patents, Design, Trademarks and Geographical Indications, Ministry of Commerce, Government of India. This is qualitative research. For the purpose of this research, the data pertains to last ten years. Using Python language, data analysis has been done by finding Correlation and Regression Analysis. The model has been run on Jupyter Notebook for Python. Findings: There is, visible upsurge in the VC investments in the last few years, much credited to the pro-active approach of the Government in creating the right ambience and the infrastructure. The flagship programs of the Government, like, Startup Mission and Make in India have yielded positive results. Pandemic did its own damage, but, post Covid-19 pandemic, there has been a considerable upward shift in the VC investments as they venture into new terrains, seeding new technologies and nurturing Startups. AS a result of this, there has been a significant jump in the number of Unicorns. There has been a quantum jump in number of VCs that have invested in India and also the deal size is consistently on the rise. Implications and Recommendations: By studying the existing research and data available, it is observed that there is asymmetry between the literature and the industry. The venture capital industry is inward cautious and there is dearth of exact deal data because of the secrecy and privacy issue, coupled with demographic and geographical shortcoming to collect the data. The role played by IVCA and other private players is, undoubtedly, worth a praise. It is recommended that further research should alienate with industry and be more methodical. Contribution and Value Added: This study will benefit, immensely, to both researchers, intending to do further research in this area, and, also to the industry in building a nexus with academia. This research has taken one step forward in building the bridge between the two. This paper fills the gap by identifying the relationship between key variables and apply statistical tools like Correlation and Regression analysis to assess the trends and contribution of venture capital investments in terms of key variables innovation and economic growth. The outcomes of this study will offer a comprehensive understanding of the fundamental elements of venture capital investments (VCI) and their influence on both innovation and the growth of the Indian economy.

Abstract PO5-19-08: Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neoHIP): An Open Label Randomized Phase II Trial

Abstract Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxics; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are explored. Methods: Patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer are being randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts receive TH-K. After enrollment of 22 pts to arm C, a prespecified interim efficacy analysis was conducted, and enrollment to this arm was subsequently terminated. Enrollment to the other arms continues with 32/58 pts enrolled to arm A and 33/58 pts enrolled to arm B as of 2/14/2023. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion per local clinical standard. The primary end point is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity. Funding sources: BCRF, Merck NCT03747120 Citation Format: Heather McArthur, Jorge Henrique Santos Leal, Isaac Chan, Nisha Unni, Stephen Shiao, Joshua Gruber, Samira Syed, Namrata Peswani, Navid Sadeghi, Glenda Delgado, Dawn Klemow, Reva Basho, Meredith Carter, Mai Badran, Nasir Qureshi, Jessica Curtin, Joshua Weese, Stephanie Rice, Michelle Phillips, David Chan, Hugo Hool, Dorothy Park, Mary El-Masry, Philomena McAndrew, Swati Sikaria, Laura Spring, Aditya Bardia, Mourad Tighiouart, Farnaz Dadmanesh, Armando Giuliano, Katherine Sanchez, David Page. Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neoHIP): An Open Label Randomized Phase II Trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-08.

Abstract PO5-19-05: A Phase II Trial of Stereotactic Body Radiation Therapy and Fluoroestradiol Positron Emission Tomography in Patients with Oligoprogressive Estrogen Receptor Positive Metastatic Breast Cancer

Abstract Background: The term oligoprogression (OP) refers to a clinical scenario in which patients with diffuse metastatic disease on systemic therapy have a limited number of metastases that have progressed or are new whereas the majority of metastases are stable or improved. OP disease is increasingly being encountered in clinical practice due to improvements in systemic therapy. Treating OP disease with local ablative therapies may therefore prolong the time to more diffuse progression necessitating a change in systemic therapy and may therefore lead to improved overall survival in these patients. Only one study has evaluated the role of SBRT in patients with OP MBC. This trial accrued 47 patients with OP MBC, with 2/3 having triple negative disease. There was no difference in PFS between patients that received SBRT versus those that did not (4.2 months vs. 4.4 months, p=0.2). Whether ablative therapies are beneficial in subtypes of breast cancer that have many effective systemic therapies available, such as ER+ breast cancer, remains an open question and an unmet clinical need. Design: Phase II study for patients with OP ER+ MBC (1-4 new and/or progressing metastatic lesions). Eligible patients will receive stereotactic body radiation therapy (SBRT) to the OP lesions. SBRT will be delivered to each lesion in 3-5 fractions. Each patient’s systemic therapy regimen will be held during study therapy and will resume upon completion of study therapy. Patients will then be restaged at 12 weeks post-SBSRT. Patients that have at least stable disease at that time point will continue on their systemic therapy and then be re-staged 12 weeks later (24 weeks after SBRT). This study will also study the role of ER-targeted positron emission tomography (PET) imaging with 16α-18F-Fluoro-17β-Fluroestradiol (FES) in the OP ER+ patient population with FES PET scans obtained at baseline, and at each of the 2 follow-up imaging timepoints. A key secondary hypothesis is that the use of FES PET in addition to standard imaging at baseline and in follow-up will help confirm patients have OP disease and will help assess for new lesions on subsequent restaging. Eligibility: Key inclusion criteria: age≥18 yo; histologically confirmed ER+/HER2- metastatic breast cancer; the presence of metastatic breast cancer at the time of study entry with progression in 1-4 lesions (including new lesions); SBRT must be feasible for all progressing lesions. Key Exclusion Criteria: >2 lines of systemic therapy for metastatic disease; intracranial disease progression Objective: To determine whether using SBRT to treat OP lesions allows ER+ breast cancer patients to continue on their current systemic therapy for at least 24 weeks post SBRT. Objective: To assess whether FES-PET increases the number of lesions found prior to SBRT; To determine the impact of SBRT on patient quality of life; time to next line systemic therapy; PFS Statistical Methods Simon 2 stage optimal design with α=0.05 and 1-β=0.80. The null hypothesis is that the proportion of patients that remain on their original systemic therapy ≥24 weeks (2 restaging scans) post-treatment is 20%. The alternative hypothesis is that the proportion of patients that remain on their original systemic therapy after 2 restaging scans is 50%. In stage 1, 8 patients that proceed to SBRT will be enrolled. The study will be terminated if only 0 or 1 subjects remain on original systemic therapy after 2 restaging scans. However, if ≥2 patients remain on original systemic therapy after 2 restaging, then an additional 10 patients would be enrolled for a total of 18 patients. The null hypothesis will be rejected if ≥6 patients remain on their original systemic therapy after 2 restaging scans. Contact Information: Jose G. Bazan (jbazan@coh.org) Funding Source: City of Hope Comprehensive Cancer Center Citation Format: Jose Bazan, Joanne Mortimer, Yun-Rose Li. A Phase II Trial of Stereotactic Body Radiation Therapy and Fluoroestradiol Positron Emission Tomography in Patients with Oligoprogressive Estrogen Receptor Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-05.

Abstract PO5-19-07: A Single Arm Phase 2 Study of Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer

Abstract Background: Triple negative breast cancer (TNBC) is a biologically distinct subtype with a high risk of early relapse. Patients not achieving a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a 3-year event free survival (EFS) of < 60%. Approximately 1/3 of patients receiving NAC with pembrolizumab-mediated immune therapy will not achieve a pCR and of those, approximately 1/3 will experience a recurrence within 3 years. Physical disruption of tumors with local strategies such as cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. The combination of cryo with immune checkpoint inhibition (ICI) has been shown to induce tumor regression and prevented tumor re-challenge in pre-clinical models. Clinical studies have also demonstrated that the combination of pre-operative cryo with ICI is safe in women with operable, early-stage breast cancer and generates intra-tumoral and systemic immune responses (NCT01502592, NCT02833233). This multi-center, single arm, phase 2 study is currently evaluating the impact of cryo with standard-of-care pembrolizumab (pembro) in women with residual TNBC after taxane-based NAC, a group at high risk of early relapse (NCT03546686). Methods: Eligible women are ≥18y, with ER < 10%, PR < 10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Pts undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and receive peri-operative pembro per standard-of-care. Adjuvant capecitabine or olaparib is recommended for all patients per local standard-of-care. Patients are stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status (positive versus negative). The primary endpoint is 3-year Event Free Survival (EFS). Secondary endpoints include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity. Funding sources: Conquer Cancer Foundation, Breast Cancer Research Foundation, Boston Scientific Citation Format: Heather McArthur, Elizabeth Comen, Yolanda Bryce, Stephen Solomon, Sangeetha Reddy, Isaac Chan, Baṣak Dogan, Dawn Klemow, Nisha Unni, Jorge Henrique Santos Leal, Cristal Martinez, Reva Basho, Dorothy Park, Philomena McAndrew, Brigid Larkin, David Page, William Mills, Staci Mellinger, Nicole Fredrich, Nicole Moxon, Lynette Currie, Meredith Carter, Melissa Ramos, Stephanie Rice, Sujata Patil, Margaret Gatti-Mays, Larry Norton. A Single Arm Phase 2 Study of Peri-Operative Immune Checkpoint Inhibition and Cryoablation in Women With Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-07.

Abstract PO2-17-12: Phase I Trial of alpha-lactalbumin vaccine in high risk operable triple negative breast cancer (TNBC) and patients at high genetic risk for TNBC

Abstract Background: Triple-negative breast cancer (TNBC) has a poor prognosis and may be associated with germline mutations. α-Lactalbumin (aLA) is expressed in lactating breasts but not at other times or in other tissues. Expression of aLA is found in 70% of TNBC (PMID: 27322324) so could be an immunologic target for TNBC based on the “retired protein hypothesis” (PMID: 31926646). In pre-clinical studies, vaccination with aLA provided protection from development of autochthonous tumors in transgenic murine models of breast cancer and inhibited growth of established 4T1 transplantable breast tumors in BALB/c mice (PMID: 20512124). Methods: To determine the safety and immunogenicity of aLA, patients with early stage TNBC are being entered in a Phase I trial of aLA with GMP-grade zymosan adjuvant in Montanide ISA 51 VG vehicle. Subjects receive 3 vaccinations given once every 2 weeks. Events of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 are considered dose-limiting toxicities (DLTs). Results: CTCAE toxicity by dose level is summarized below. All DLTs were injection site reactions, with ulceration and need for incisional drainage representing the grade 3 events. Seven (7) of 10 patients assayed to date have met protocol specified definitions of an immune response based on ELISpot assays to determine frequencies of T cells producing IFNγ and IL-17 in response to recombinant aLA. Assays for an additional 6 patients will be available in September 2023. Conclusion: Dose level ≤ 2 appears to be the maximum tolerated dose. Based on immune response, additional intermediate dose levels may be studied. An additional cohort of patients receiving concurrent anti-PD1 treatment is being accrued. Accrual of patients with BRCA1/2 or PALB2 mutations planning to undergo prophylactic mastectomy is beginning in order to define the toxicity and immunologic effects in this group and to determine whether inflammatory changes from occult lactational foci will be produced. Funding Source: Department of Defense (W81XWH-17-1-0592 and W81XWH-17-1-0593) Table 1 Worst Toxicity by Dose Level Citation Format: Justin Johnson, Emily Rhoades, Holly Levengood, Halle Moore, Megan Kruse, Erin Roesch, Jame Abraham, Brenna Elliott, Rachel Swartz, Holly Pederson, Elena Haury, Azka Ali, Tiffany Onger, Andrew Sciallis, Zahraa Al-Hilli, Wei Wei, Thaddeus Stappenbeck, George Budd. Phase I Trial of alpha-lactalbumin vaccine in high risk operable triple negative breast cancer (TNBC) and patients at high genetic risk for TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-12.

Abstract PO3-20-04: A first-in-human study of the highly selective PI3Kα inhibitor RLY-5836 in patients with advanced breast cancer and other solid tumors

Abstract Background: Oncogenic activation of PI3Kα is a common driver event in solid tumors. Although PI3Kα is a validated therapeutic target, there is no approved highly selective inhibitor that targets mutant PI3Kα. Alpelisib, a non-selective orthosteric PI3Kα inhibitor, is approved in combination with fulvestrant for patients with PIK3CA-mutant, ER+, HER2– advanced breast cancer. Inhibition of wild-type PI3Kα causes hyperglycemia, limiting the tolerability, dosing, and efficacy of alpelisib. RLY-5836 is the second allosteric, selective pan-mutant PI3Kα inhibitor under clinical investigation. It is molecularly distinct with differentiated pharmaceutical properties compared to RLY-2608. This first-in-human study aims to further explore the tolerability and efficacy of highly selective PIK3CA-mutant inhibition as monotherapy and in combination treatment. Methods: This multicenter, open-label study is designed to evaluate the safety, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), pharmacokinetics (PK) and preliminary anti-tumor efficacy of RLY-5836 as a single agent and in various combinations. A Bayesian Optimal Interval design is used for dose escalation, followed by a dose expansion part. As monotherapy, RLY-5836 will be investigated in pts with advanced solid tumors harboring a PIK3CA mutation (Arm 1) per local assessment (blood and/or tumor). In pts with PIK3CA-mutant, HR+, HER2– advanced or metastatic breast cancer, RLY-5836 combination arms will include anti-estrogen therapy with or without CDK4/6 inhibition: fulvestrant (Arm 2), and fulvestrant + CDK4/6 inhibitor(s) (Arms 3–5). RLY-5836 is administered orally, continuously in 28-day cycles until disease progression or study discontinuation. Enrollment criteria include age ≥18 years, ECOG PS 0–1, and measurable disease (Arm 1) or evaluable disease (Arms 2–5) per RECIST version 1.1. Participants in the combination arms are required to have received prior treatment with ≥1 CDK4/6 inhibitor and ≥1 anti-estrogen therapy. Prior treatment with a PI3Kα inhibitor is an exclusion criterion for the dose expansion parts of all arms. Planned overall sample size is ~220 pts (~145 pts for the dose escalation, and ~15 pts in each dose expansion arm). Primary endpoints are the MTD, RP2D and overall safety profile of RLY-5836, either as a single agent or in combination. The MTD will be determined as the dose with a dose-limiting toxicity rate closest to the target toxicity rate (30%) in Cycle 1. Secondary endpoints include PK and efficacy parameters. Statistical analyses will be descriptive. This study (NCT05759949) is enrolling in the United States. For further information, please contact clinicaltrials@relaytx.com. Funding source: This study is funded by Relay Therapeutics, Cambridge, MA, United States. Citation Format: Andreas Varkaris, Steven Isakoff, Cesar A. Perez, Bert O'Neil, Erika Hamilton, Erin Conlin, Gege Tan, Xiaoyan Li, Alison Timm, Ramin Samadani, Erika Puente-Poushnejad, Eunice Kwak, Brenton G. Mar, Alison M. Schram. A first-in-human study of the highly selective PI3Kα inhibitor RLY-5836 in patients with advanced breast cancer and other solid tumors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-04.

The most fundamental and popular literature on functional near-infrared spectroscopy: a bibliometric analysis of the top 100 most cited articles

BackgroundFunctional near infrared spectroscopy (fNIRS) has developed rapidly in recent years, and there are more and more studies on fNIRS. At present, there is no bibliometric analysis of the top 100 most cited articles on fNIRS research.ObjectiveTo identify the top 100 most cited articles on fNIRS and analyze those most fundamental and popular articles through bibliometric research methods.MethodsThe literature on fNIRS of web of science from 1990 to 2023 was searched and the top 100 most cited articles were identified by citations. Use the bibliometrix package in R studio and VOSviewer for data analysis and plotting to obtain the output characteristics and citation status of these 100 most cited articles, and analyze research trends in this field through keywords.ResultsA total of 9,424 articles were retrieved from web of science since 1990. The average citation number of the 100 articles was 457.4 (range from 260 to 1,366). Neuroimage published the most articles (n = 31). Villringer, A. from Leipzig University had the largest number of top 100 papers. Harvard University (n = 22) conducted most cited articles. The United States, Germany, Japan, and the United Kingdom had most cited articles, respectively. The most common keywords were near-infrared spectroscopy, activation, cerebral-blood-flow, brain, newborn-infants, oxygenation, cortex, fMRI, spectroscopy. The fund sources mostly came from National Institutes of Health Unitd States (NIH) and United States Department of Health Human Services (n = 28).ConclusionNeuroimage was the most popular journal. The top countries, institutions, and authors were the United States, Harvard University, and Villringer, A., respectively. Researchers and institutions from North America and Europe contributed the most. Near-infrared spectroscopy, activation, cerebral-blood-flow, brain, newborn-infants, oxygenation, cortex, fmri, spectroscopy, stimulation, blood-flow, light-propagation, infants, tissue comprise the future research directions and potential topic hotspots for fNIRS.

Abstract PO1-06-14: Preliminary results of a phase I dose escalation study of eribulin in combination with copanlisib in patients with metastatic triple negative breast cancer (TNBC)

Abstract Background: Aberrant PI3K pathway signaling is frequently observed in TNBC. Increasing evidence indicate that PI3K pathway activation maintains the stemness and chemoresistance of breast cancer stem cells (CSCs). PI3K inhibition sensitizes CSCs to chemotherapy. Eribulin (E), a non-taxane microtubule dynamics inhibitor, showed overall survival benefit in metastatic HER2 negative BC. Preclinically, the addition of copanlisib (C), a potent pan-class I PI3K inhibitor that is highly selective against α and δ PI3K isoforms, improved anti-tumor effect in both E-sensitive and resistant TNBC patient-derived xenograft models, irrespective of PIK3CA/PTEN alteration status. Here we report the preliminary data of the phase I dose escalation trial of E+C in patients with metastatic TNBC. Methods: This trial includes a phase I study to determine the dose limiting toxicity (DLT) and recommended phase 2 dose (RP2D) of E+C, followed by a randomized phase II study of E+C (at RP2D) versus E (stratified by tumor PIK3CA/PTEN mutation status) with progression-free survival (PFS) as the primary endpoint. Key eligibility included patients with: metastatic TNBC who progressed on ≤5 lines of chemotherapy, prior anthracycline/taxane chemotherapy (unless contraindicated), ECOG 0-1, adequate organ function and known tumor PIK3CA/PTEN/AKT mutation status. Key exclusions include: prior receipt of E or any PI3K/mTOR/AKT inhibitor, grade ≥2 neuropathy, presence of tumor AKT mutation, and uncontrolled diabetes, hypertension or congenital QT prolongation. A 3+3 design was used to determine the DLT and RP2D. Dose level 1 (DL1) started with E at 1.1 mg/m2 mg IV and C at 45 mg IV on days (D) 1/8 of 21-D cycle, with the potential to escalate to 2 additional dose levels – DL2: E 1.4 mg/m2 and C 45 mg on D 1/8; DL3: E 1.4 mg/m2 and C 60 mg on D 1/8. Results: Eight patients were enrolled in the phase I study and received at least 1 dose of E+C. The median age was 48.5 (range, 26-67) years. The majority of patients identified as White (additionally 2 Hispanic, 1 Black) and had an ECOG performance status of 1 (n=6, 75.0%). Tumor PIK3CA and PTEN alterations were each observed in 1 patient. Median number of cycles received were 2 (range, 1-5). All 8 patients had at least 1 treatment-related adverse event (TRAE). The most common TRAEs across all dose levels were: lymphopenia (n=5, 62.5%), neutropenia (n=5, 62.5%), hyperglycemia (n=4, 50.0%), anemia (n=4, 50.0%) and fatigue (n=4, 50.0%); most toxicities were grade (G) 1-2. G3 hyperglycemia and hypertension were observed in 1 patient each, were medically managed and did not lead to treatment interruption. 1 patient was diagnosed with pulmonary embolism, possibly attributed to study therapy and breast cancer. DLTs were reported in 2 of 2 patients treated at DL2 - 1 patient developed G3 rash responsive to oral corticosteroids, and 1 patient developed G3 acute kidney injury in the setting of hypovolemia and discontinued study therapy. No additional patients were enrolled in DL2. No DLTs were observed in all 6 patients treated at DL1. 1 patient treated at DL1 had possible G1 non-infectious pneumonitis that resolved spontaneously on short interval imaging. Stable disease was observed in 2 of 6 response-evaluable patients (33.3%). 1 patient achieved regression of cutaneous disease following 1 cycle of therapy as assessed by the treating investigator. DL1, E at 1.1 mg/m2 plus C at 45 mg IV, was determined to be the RP2D. Tumor tissue biomarker analysis is underway. Conclusion: These data indicate that E+C at DL1 is a well-tolerated regimen warranting further investigation. The study is actively enrolling patients to the phase II study. Clinical trial information: NCT04345913. Funding Source: National Cancer Institute. Citation Format: Nusayba Bagegni, Brittney Haas, Leslie Nehring, Jingqin Luo, Laura Kennedy, Meghna Trivedi, Manali Bhave, Rabih Said, Cynthia Ma. Preliminary results of a phase I dose escalation study of eribulin in combination with copanlisib in patients with metastatic triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-06-14.

Abstract PO3-20-03: First-in-human global study of RLY-2608, a pan-mutant and isoform selective PI3Kα inhibitor, as a single agent in patients with advanced solid tumors and in combination with fulvestrant in patients with advanced breast cancer

Abstract Background: Oncogenic mutations in PI3Kα are common driver events in ER+ breast cancer and other solid tumors. Alpelisib, a non-mutant selective PI3Kα inhibitor, is effective in ER+ breast cancer thus validating PI3Kα as a therapeutic target. Inhibition of wild-type PI3Kα results in toxicity including hyperglycemia which limits tolerability and drug exposure. RLY-2608, a novel, oral allosteric PI3Kα inhibitor, is uniquely designed to overcome these limitations via mutant- and isoform-selective PI3Kα inhibition for greater target coverage, improved tolerability, and antitumor activity. Initiated in December 2021, ReDiscover is the ongoing, first-in-human study to define the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of RLY-2608 monotherapy in PIK3CA-mutant advanced solid tumor patients (pts) and of RLY-2608 plus fulvestrant in pts with PIK3CA-mutant, HR+HER2-BC. At AACR 2023, dose escalation data for RLY-2608 was reported and demonstrated encouraging target inhibition and anti-tumor activity (including partial response), across PIK3CA genotypes with minimal impact on glucose homeostasis. To date, pts have received RLY-2608 at doses of 100–2000 mg/day, with no reported dose-limiting toxicities; the MTD has not been reached. These proof-of-mechanism data indicate that RLY-2608 is the first allosteric, pan-mutant selective PI3Kα inhibitor and that RLY-2608 has broad therapeutic potential in PIK3CA-driven cancers. Methods: Enrollment is ongoing in this global, multi-center, dose escalation/expansion study of RLY-2608 as a single agent in adults who have advanced solid tumors and are refractory, intolerant, or have declined standard therapy; and RLY-2608 in combination with fulvestrant in previously treated pts with HR+/HER2– MBC. Eligibility criteria include presence of PIK3CA mutation (blood or tumor) per local assessment, ECOG performance status 0–1, evaluable disease per RECIST 1.1 and no prior PI3K inhibitor (except in expansion combination group 2). RLY-2608 is administered on a continuous schedule with 4-week cycles. Adverse events (AEs) per CTCAE v5, PK, biomarkers (pAKT, mutant ctDNAs and insulin pathway markers) and anti-tumor activity are assessed serially. Dose escalation employs a Bayesian Optimal Interval design to identify the MTD and/or the recommended Phase 2 dose (RP2D). Following dose escalation, expansion cohorts will enroll patients with select PIK3CA-mutated solid tumors for treatment with RLY-2608 monotherapy and patients with HR+/HER2– MBC for treatment with RLY-2608 and fulvestrant. The primary endpoints are MTD/RP2D and AE profile for single agent and combination; key secondary endpoints are PIK3CA genotype in blood and tumor, PK, biomarkers, and overall response rate. ReDiscover (NCT05216432) is enrolling worldwide. For further information, contact clinicaltrials@relaytx.com. Funding source: This study is funded by Relay Therapeutics, Cambridge, MA, United States. Citation Format: Andreas Varkaris, Komal Jhaveri, Elena Garralda Cabanas, Lucia Sanz, Janice Kim, Cesar A. Perez, Erika Hamilton, Alexander I. Spira, Kari Wisinski, Angel Guerrero, Jason Henry, Jordi Rodon Ahnert, Gege Tan, Xiaoyan Li, Diana Hummel, Tamieka Hunter, Alison Timm, Ramin Samadani, Erika Puente-Poushnejad, Eunice Kwak, Brenton G. Mar, Alison M. Schram. First-in-human global study of RLY-2608, a pan-mutant and isoform selective PI3Kα inhibitor, as a single agent in patients with advanced solid tumors and in combination with fulvestrant in patients with advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-03.

Abstract PO1-10-12: Advancing Gender Equity: A Closer Look at Women's Representation in Leading Breast Cancer Clinical Trials

Abstract Introduction: Clinical trials serve as pivotal sources for evidence-based medicine, wielding substantial influence within the medical and scientific community. In recent years, heightened attention has been directed towards encouraging greater female involvement and advancing their representation across various domains of the medical field. Female oncologists tend to focus more over breast cancer as a subspeciality and focused practice. Consequently, this observational study seeks to assess the present status of gender equity in leading breast cancer clinical trials, with the aim of identifying potential concerns and mitigating future risks of bias. By delving into this analysis, we can shed light on the current landscape and pave the way for improved inclusivity and fairness in breast cancer research. Methodology: To examine the portrayal of female principal investigators (PIs) in breast cancer clinical trials over the past two decades, we conducted a thorough search of breast cancer clinical trials listed on ClinicalTrials.gov. Furthermore, we employed https://gender-api.com to assess the gender of each PI and calculate the experience in the medical field of the PI by subtracting the PI graduation year from the year of conducting the clinical trial. In addition, we gathered pertinent details concerning the PIs and the clinical trials, and subsequently subjected the data to univariate analyses to detect any noteworthy distinctions between male and female PIs. Results: Over the span of the past twenty years, a total of 9,145 cancer clinical trials were conducted, with 1,127 (12.32%) focusing specifically on breast cancer. Through our rigorous efforts, we managed to gather comprehensive information about the principal investigators (PIs) in 788 (69.92%) of these clinical trials. Notably, we discovered that 419 (53.17%) of these trials were led by female investigators. Upon scrutinizing the characteristics of the PIs, we observed several significant distinctions between male and female PIs. Female PIs exhibited a lower median age (57.0 vs. 60.0) and possessed less medical experience (17 vs. 22 years) compared to their male counterparts (P< 0.001). Furthermore, we found a substantial divergence in the funding sources for the clinical trials between the genders. Female-led trials received a lower percentage of industrial funding (13.1% vs. 24.2% for males, P< 0.001) but showcased a significantly higher percentage of university funding (38.7% vs. 28.0% for males, P< 0.001). Most of the clinical trials led by female PIs were categorized as phase 2 trials (82.8% vs. 66.8% for males) and were conducted in single centers (61.2% vs. 52.6% for males), demonstrating a noteworthy statistical difference (P< 0.001) in both cases. However, no statistically significant disparities were found between male and female PIs in terms of termination rates, publication rates, or the type of intervention utilized in the clinical trials. Furthermore, the ratio of females PI wasn’t different throughout the time as the liner regression model estimated effect was -0.009 with P= 0.065. Conclusions: The study shows the great effort done by female researchers, even though they have lower age, experience, and support from the industrial companies and lower opportunity to have bigger multicenter clinical trials, they still manage to have equivalent rate of termination and publication of the clinical trials showing their capability to lead clinical trials and the need to be supported to maintain the gender equity in leading the breast cancer clinical trials. However, female involvement in other cancer sites might be different and needs to be looked at. Citation Format: Abdulrahman Alhajahjeh, Ghayda’ Bader, Basil Abdin, Taima’ Bader, Saji Aweidah, Layla El-Amayreh, Hikmat Abdel-Razeq. Advancing Gender Equity: A Closer Look at Women's Representation in Leading Breast Cancer Clinical Trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-12.

Share pledging: Measuring margin call pressure and its influence on liquidity commonality

AbstractWhile share pledging is a widespread leveraged financing practice in global stock markets, its potential impact on firms' exposure to market risk remains a topic of concern. In the context of the Chinese market, this study investigates the relationship between insiders' share pledging pressure and stock liquidity risk, with a particular focus on stock liquidity commonality. Using data from Chinese firms listed between 2009 and 2022, we find a positive correlation between heightened share pledging pressure and increased stock liquidity commonality. To precisely capture the margin call pressure arising from share pledging, we introduce an innovative method that considers both the price at which shares are pledged and their subsequent price dynamics. This relationship persists after addressing endogeneity concerns. Furthermore, we find that firms under significant share pledging pressure often resort to earnings manipulation, which exacerbates stock liquidity commonality. The findings underscore the significance of understanding the risks and impacts of share pledging in terms of liquidity risk. Insiders who utilize share pledging as a financing channel face a delicate balance between the benefits of expanded funding sources and the risks of losing control due to sustained stock price declines. This study provides valuable insights for investors, policymakers, and regulatory authorities in managing the potential liquidity risks associated with share pledging activities in the Chinese market.

An ecosystem approach to mentoring research faculty in schools of nursing: The pacific northwest interdependence mentoring model

BackgroundMentoring can facilitate faculty career development and retention. Given ongoing challenges in academic nursing (e.g., shrinking number of experienced mentors), it is necessary to revisit and improve upon existing mentoring models and practices to support current and future nurse researchers. PurposeTo describe the development of a new faculty-to-faculty research mentoring model. MethodsConstruction of a model describing mentoring needed by research-focused nurse faculty based on analysis of the literature alongside the authors’ personal experiences. FindingsThe Pacific Northwest Interdependence Mentoring Model (PIMM) describes academic nursing as an ecosystem that fosters caring, trust, solidarity, equity, openness, and interdependent relationships among research faculty, administration, institutions, and funding sources. DiscussionAlthough mentoring environments differ in unique strengths, weaknesses, mission, culture, and values, the PIMM’s approach could be applicable for many schools of nursing and beyond to support the growth of the nursing discipline.

Climate finance opportunities for health and health systems.

Climate change poses significant risks to health and health systems, with the greatest impacts in low- and middle-income countries - which are least responsible for greenhouse gas emissions. The Conference of Parties 28 at the 2023 United Nations Climate Change Conference led to agreement on the need for holistic and equitable financing approaches to address the climate and health crisis. This paper provides an overview of existing climate finance mechanisms - that is, multilateral funds, voluntary market-based mechanisms, taxes, microlevies and adaptive social protection. We discuss these approaches' potential use to promote health, generate additional health sector resources and enhance health system sustainability and resilience, and also explore implementation challenges. We suggest that public health practitioners, policy-makers and researchers seize the opportunity to leverage climate funding for better health and sustainable, climate-resilient health systems. Emphasizing the wider benefits of investing in health for the economy can help prioritize health within climate finance initiatives. Meaningful progress will require the global community acknowledging the underlying political economy challenges that have so far limited the potential of climate finance to address health goals. To address these challenges, we need to restructure financing institutions to empower communities at the frontline of the climate and health crisis and ensure their needs are met. Efforts from global and national level stakeholders should focus on mobilizing a wide range of funding sources, prioritizing co-design and accessibility of financing arrangements. These stakeholders should also invest in rigorous monitoring and evaluation of initiatives to ensure relevant health and well-being outcomes are addressed.

The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ

PolyQ diseases are autosomal dominant neurodegenerative disorders caused by the expansion of CAG repeats. While of slow progression, these diseases are ultimately fatal and lack effective therapies. A high-throughput chemical screen was conducted to identify drugs that lower the toxicity of a protein containing the first exon of Huntington's disease (HD) protein huntingtin (HTT) harbouring 94 glutamines (Htt-Q94). Candidate drugs were tested in a wide range of invitro and invivo models of polyQ toxicity. The chemical screen identified the anti-leprosy drug clofazimine as a hit, which was subsequently validated in several invitro models. Computational analyses of transcriptional signatures revealed that the effect of clofazimine was due to the stimulation of mitochondrial biogenesis by peroxisome proliferator-activated receptor gamma (PPARγ). In agreement with this, clofazimine rescued mitochondrial dysfunction triggered by Htt-Q94 expression. Importantly, clofazimine also limited polyQ toxicity in developing zebrafish and neuron-specific worm models of polyQ disease. Our results support the potential of repurposing the antimicrobial drug clofazimine for the treatment of polyQ diseases. A full list of funding sources can be found in the acknowledgments section.

Public Funds as a Source of Financing Revalorization of Sacral Historical Monuments: The Example of Poland

Sacral historical monuments are primarily places of prayer, but also objects performing numerous other functions. These are public goods, including cultural goods that build national identity. Their preservation in the right condition is important not only for the owner, but also for the public authorities, whose duty is to preserve them for future generations. The study concerns the financing of sacral monuments in Poland. Its aim is to indicate the legitimacy of financing the revalorization of sacral monuments from public funds, the solutions applied in this area in Poland, and the sources and amount of support provided to the owners of these objects in the years 2017–2022. In it, the authors: (1) refer to such concepts as: public good, cultural good and cultural heritage, (2) define—based on Polish regulations—the concept of a sacral monument and indicate the multiplicity of functions that these objects perform, (3) present the number and types of sacral monuments in Poland, taking into account their location, (4) identify available sources of public funds for the revalorization of sacral monuments in Poland. The analyses carried out show that in Poland, every year, public funds play an important role in the revalorization of sacral historical monuments. In real terms, its volume remained at a similar level over the period considered. The methods used in the development are as follows: critical analysis of the literature and legal acts and selected methods of descriptive statistics.

Strategy For Fulfilling Resources and Managing Education Financing in Primary Schools

One of the important problems in educational development in almost every country in the world is education financing. Education financing is an activity related to obtaining the funds received and how these funds are used to finance all educational programs that have been determined. This research aims to determine the sources of education financing and how elementary school education financing is managed in Blora Regency. The method used in this research is qualitative method. The research was conducted in three elementary schools in Blora Regency. The data collection method in this research was carried out in three ways, namely: interviews, observation, and documentation. The research results are: (1) Fulfillment of funding sources for primary school education in Blora Regency comes from three main sources, namely: central government, regional government, and the community; (2) Management of primary school education financing in Blora Regency has been carried out in three stages, namely: planning education financing, implementing education financing and evaluating education financing.

Towards higher standardization of funding acknowledgements in scientific publications: Current status in the case of a national and a European research fellowship scheme

Abstract Acknowledgement of funding sources in scientific publications is becoming mandatory in science. As funders' instructions are often vague, there is great variability in the way authors acknowledge funding, this hindering the linking of grants to their subsequent publications. The aim of this study is to analyse how funding is acknowledged in scientific publications in two important research fellowship schemes: the Spanish Ramón y Cajal programme (RyC) and the European Marie Skłodowska-Curie Research Actions (MSCA). WoS publications in 2017 by Spain-based researchers that include funding acknowledgements from either of the two programmes are identified. Firstly, compliance with funders’ recommendations in terms of the elements included in acknowledgements is analysed. Secondly, the degree of comprehensiveness in the authors’ description of the grants is studied by focusing on how often different items are reported (funding agency, programme, grant number, grantee, year of the call, etc). Thirdly, the use of normalized structured notations in acknowledgements is examined. Around 78% of RyC vs. 84% of MSCA grants comply with funders’ recommendations regarding the elements to be included in the acknowledgements. A comprehensive description of grants is unusual in both programmes. Structured notations are included in two-thirds of RyC vs. one-third of MSCA grants. Advantages of using structured notations are highlighted, since they provide unique identification of grants, improve the comprehensiveness and normalization of funding data, facilitate automatic data processing and could be compatible with global grant identifiers. Further standardization of funding data in acknowledgements is needed to optimize their use in science policy studies.

PUBLIC-PRIVATE PARTNERSHIP AS A TOOL FOR FINANCIAL SUPPORT OF THE ENERGY SECTOR IN UKRAINE: ANALYSIS, MECHANISM, FINANCIAL REPORTING

Based on the analysis of the dynamics of implementation of public-private partnership (PPP) projects in Ukraine, key problems have been identified and its priorities in financial support for the recovery of the native energy sector have been determined. It is appointed that PPP concession agreements are the main mechanisms for attracting investment in the global electric power industry. The expediency of using the concession model on BOT terms for the implementation of large projects in the energy sector is substantiated, which will contribute to the intensification of investment attraction and will allow to distribute risks between the state and business. Recommendations on the formation of an information platform for participants in the implementation of PPP projects on the basis of disclosure of information on the effectiveness of concession operations in accounting and financial statements have been developed. The tools for the formation of the financial mechanism of public-private partnership, where the priority is budget and venture financing, are substantiated. To make decisions on the implementation of PPP investment projects, an approach to assessing the financial support of project initiatives is recommended, the basis of which is the proposed criteria for compliance with financial security, the choice of funding sources, indicators of scenario analysis and efficiency. The proposed methodical approach to assessing the effectiveness of PPP allows us to assess the synergistic effect, which reflects the totality of economic, social and environmental effects. The formulated recommendations for improving the relationship between the state and business will contribute to the intensification of the attraction of private investment resources on the basis of PPPs for the restoration of the energy sector in Ukraine.

Victorian (Australian) parents are receptive to a primary school-provided lunch program

Purpose This study aims to examine Victorian primary school parents’ perspectives about a potential school-provided lunch program (LP). Design/methodology/approach An online cross-sectional survey was conducted in Victoria, Australia, in 2022 to explore parents’ perceptions regarding the lunch menu, funding source, amount willing to pay, frequency of meals and special dietary needs of a school-provided LP. Findings Over half of parents (57% out of 359) said they would allow their child to participate in a school LP, 34% were unsure and only 9% said they would not. The opportunity for hot cooked lunches at school and the perceived convenience for parents were the top two reasons for favouring such a program. Fifty-eight percent were in favour of hybrid-type funding from both the government and parents. The most preferred amount to pay per meal was AUD5-6 (43%), followed by AUD3-4 (25%). Parents expected meals to be healthy and made from whole food and cater to the special dietary and cultural needs of their children. They also expected enough time to be allocated so children could eat and enjoy the meals. Originality/value To the best of the authors’ knowledge, this is the first study to explore Victorian parents’ perceptions regarding the above aspects of a school-provided LP. The findings suggest that parents are receptive to a school-provided LP; they, however, did have several expectations regarding the menu and time for eating. These findings provide important directions for designing future school-provided LPs at primary schools in Australia.

Health financing analysis in the implementation of minimum service standards in Lumajang Regency

Background: Health financing in Lumajang is still far from the target. Therefore, a study focused on the implementation of minimum service standards (MSS) in the health sector is needed. Despite the government emphasis on MSS health, disparities in service access and health conditions persist.Objective: To provide insights into the effectiveness of health financing, serving as a foundation for policy recommendations to enhance the efficiency and effectiveness of health fund allocation in Lumajang Regency.Methods: The study employed a quantitative approach, utilising district health accounts (DHA) and cost and benefit analysis (CBA). The budget allocation for different MSS health services was also investigated. The analysis involved examining the spending proportion relative to total health expenditure. The study design used a qualitative descriptive method. The data source was obtained from the budget realisation report for the MSS health sub-activities at the Community Health Center (CHC) and the Lumajang Health Office. Data analysis was performed by an integration of DHA and CBA approaches. We performed mapping costs and benefits analysis and calculated the sensitivity of financing to whether it is economically profitable and provides leverage for achieving MSS performance indicator targets. Results: The realisation of local original revenue in the health sector tended to fall below targets. Central transfer funds dominated the funding sources in CHC. The highest health budget allocation of MSS was received by maternal health services, while other services only received a proportion relative to a decrease in total health expenditure.Conclusion: In Lumajang Regency, analysis of the costs and benefits of regional health financing to fulfil MSS health showed that the benefit-cost ratio (BCR) value was > 1, meaning that health financing for MSS in the District Health Sector was profitable, so it should be used as a regional priority program in overcoming regional health problems.