On December 6, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI), a clinical-stage biotechnology company developing eganelisib, a potentially first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic that selectively inhibits phosphoinositide-3-kinase gamma (PI3K-gamma), reported that it will host an investor event on updated data from the ongoing MARIO-3 clinical study during the San Antonio Breast Cancer Symposium (SABCS 2021) on Friday, December 10th at 9:30 am ET (Press release, Infinity Pharmaceuticals, DEC 6, 2021, View Source [SID1234596477]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The webinar will feature a presentation from Key Opinion Leader (KOL) Hatem Soliman, MD, MARIO-3 Investigator and Medical Director, Clinical Trials Office at the Moffitt Cancer Center.

Dr Soliman will discuss the evolving treatment landscape in TNBC and the significant unmet medical need that remains for patients with frontline, metastatic TNBC.
Importantly, Dr Soliman will review the MARIO-3 study design and summarize patient demographics and baseline characteristics as well as the updated safety and efficacy data from the MARIO-3 study.
Infinity’s Chief Medical Officer, Dr. Robert Ilaria, will review of eganelisib’s mechanism of action and translational data from the MARIO-3 study.

A Q&A session will follow the formal presentations. To register for the webinar please click here.

Hatem Soliman, MD is one of the leading breast cancer physicians in the country and an investigator on the MARIO-3 study. Dr. Soliman serves as the Medical Director of the Clinical Trials Office at the Moffitt Cancer Center, with extensive experience as a clinical investigator conducting both translational research in breast cancer immunotherapy and leading numerous clinical trials as principal investigator since joining the faculty at Moffitt in 2008. He also serves as the Course Director for the fellowship clinical research rotation, medical director of the phase 1 program, chair of Moffitt’s clinical research leadership council, chair of clinical research feasibility committee, and principal investigator for Moffitt’s CPDM CCSG application, which was recently rated as outstanding and awarded funding for an additional five years.

Dr. Soliman received his BS in Genetics from the University of Georgia Athens in 1996 and then went on to receive his medical degree from the Medical College of Georgia in 2002. His residency and fellowship training in oncology/hematology was completed through the University of South Florida/Moffitt Cancer Center program in 2008. During fellowship, he authored investigator initiated early phase trials with mentorship from Dr. Daniel Sullivan, former ACD and EVP of Moffitt, in collaboration with the NCI CTEP RAID program investigators Drs. Jaime Zwiebel and Howard Streicher. Upon graduation, Dr. Soliman was offered an assistant member position at Moffitt as a clinical investigator to continue early drug development and translational research activities.

On December 6, 2021 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the first patient has been dosed in a Phase 1b/2 trial evaluating nirogacestat, SpringWorks’ investigational gamma secretase inhibitor (GSI), in combination with elranatamab (PF-06863135) Pfizer’s investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody, in patients with relapsed or refractory multiple myeloma (Press release, SpringWorks Therapeutics, DEC 6, 2021, View Source [SID1234596493]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase the cell surface density of BCMA and reduce levels of soluble BCMA, thereby enhancing the activity of BCMA-targeted therapies, including CD3 bispecific antibodies.1,2

"We are very pleased to be dosing patients in this study, which is one of six collaborations evaluating the combination of nirogacestat with a BCMA-targeted therapy as part of our broader effort to explore our gamma secretase inhibitor’s role as a potential cornerstone of BCMA combination therapy," said Saqib Islam, Chief Executive Officer of SpringWorks. "Our goal is to improve treatment options for patients with multiple myeloma and we look forward to generating data with our collaborators to determine if adding nirogacestat can potentiate the activity of BCMA-directed therapies for these patients."

The Phase 1b/2 trial, which is one sub-study of Pfizer’s umbrella MagnetisMM-4 trial (NCT05090566), is an open-label study evaluating the safety, tolerability and preliminary efficacy of elranatamab in combination with nirogacestat in patients with relapsed or refractory multiple myeloma. The trial is being advanced pursuant to a clinical trial collaboration agreement between SpringWorks and Pfizer. Under the terms of the agreement, Pfizer is sponsoring and conducting the Phase 1b/2 study and is assuming all costs other than expenses related to the manufacturing of nirogacestat and certain expenses related to intellectual property rights. The companies have formed a joint development committee to manage the clinical study.

About Elranatamab

Elranatamab is an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody being investigated in relapsed or refractory multiple myeloma. Binding affinity to BCMA and CD3 has been optimized, to potentially elicit more potent T-cell-mediated anti-myeloma activity. Elranatamab is being investigated as a subcutaneous administration, which is intended to allow higher doses than intravenous administration without increasing adverse events.

Elranatamab has been granted Orphan Drug Designations by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of multiple myeloma. The U.S. FDA and EMA have also granted elranatamab Fast Track Designation for the treatment of patients with multiple myeloma who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody and the PRIME scheme for the treatment of multiple myeloma, respectively.

About Nirogacestat

Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has six collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, two CAR T cell therapies, two bispecific antibodies and a monoclonal antibody. SpringWorks has also formed research collaborations with Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA therapies using a variety of preclinical multiple myeloma models.

Nirogacestat has received Orphan Drug Designation from the U.S. FDA for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.

On December 6, 2021 GRAIL, LLC, a healthcare company whose mission is to detect cancer early when it can be cured, reported a partnership with Alignment Health Plan, a national Medicare Advantage health plan from Alignment Healthcare (NASDAQ: ALHC), to provide its Medicare Advantage members access to Galleri, GRAIL’s groundbreaking multi-cancer early detection blood test (Press release, Grail, DEC 6, 2021, View Source [SID1234596509]). Based in Orange, California, Alignment Health Plan is the first Medicare Advantage plan to offer the Galleri test as a complement to recommended single cancer screenings.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Providing innovative benefits to support the health and care needs of our members is what we do here at Alignment," said Dawn Maroney, markets president, Alignment Healthcare, and CEO, Alignment Health Plan (CA). "Taking preventive measures before signs and symptoms appear is key to finding cancer early when it is most treatable. We are excited to partner with GRAIL to provide seniors the tools they need to proactively manage their health."

New and existing Alignment Health Plan members who enroll in select HMO and PPO plans in California and North Carolina1 will have access to Galleri beginning Jan. 1, 2022. Galleri is available by prescription only.

"GRAIL is thrilled to partner with Alignment Health Plan to offer our first-of-its-kind Galleri test to a population that by age alone has an elevated risk of developing cancer," said Dr. Josh Ofman, president and chief medical officer at GRAIL. "Providing access to a technology that can detect cancer signals in the blood, even before symptoms appear, can help us decrease the burden of late-stage cancer diagnoses. We commend Alignment for its innovative and proactive approach to early cancer detection for Medicare Advantage members."

In a clinical study, Galleri demonstrated the ability to detect more than 50 types of cancer, over 45 of which lack recommended screening tests today, with a low false positive rate of less than 1%. When cancer is detected, Galleri can determine the cancer signal origin with high accuracy.

More than 600,000 people died from cancer last year in the United States, according to the American Cancer Society. This is in large part because the majority of cancers are found too late when outcomes are often poor. Recommended screening tests save lives, but only cover five cancer types in the U.S.: breast, colon, cervical, prostate, and (in high-risk adults) lung. In fact, about seven in ten cancer deaths have no recommended early detection screening.

On December 6, 2021 Carisma Therapeutics., a clinical stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that it has entered into a clinical study collaboration with Merck (known as MSD outside the US and Canada) to evaluate their proprietary targeted chimeric antigen receptor macrophages (CAR-M) in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) for the treatment of human epidermal growth factor receptor 2 (HER2) overexpressing cancers (Press release, Carisma Therapeutics, DEC 6, 2021, View Source [SID1234596529]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Based on pre-clinical findings outlined in Human chimeric antigen receptor macrophages for cancer immunotherapy, Carisma’s novel CAR-M platform has the potential ability to reprogram the solid tumor microenvironment, leading to immune activation, T cell recruitment, and anti-tumor adaptive immunity.

"The mechanisms of action behind CT-0508 and KEYTRUDA suggest they may be complementary and could help to drive meaningful clinical benefits in patients with HER2 positive cancers, where a high unmet medical need exists," said Steven Kelly, President and Chief Executive Officer at Carisma Therapeutics. "We are extremely pleased to enter into this collaboration with Merck and further expand the potential of macrophage-based cell therapy."

This collaboration announcement comes on the heels of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting where lead investigators shared early data from the landmark Phase 1 multi-center clinical trial of CT-0508, a human epidermal growth factor receptor 2 (HER2) targeted CAR-M. The preliminary findings represent the first clinical data with genetically engineered macrophages in humans and demonstrated that CT-0508 was well tolerated after infusion and there were no dose limiting toxicities; data show the immunotherapy was successfully manufactured using macrophages obtained from heavily pre-treated, advanced solid tumor patients and showed high CAR expression, viability, and purity; and that the administered therapy remodeled the tumor microenvironment and mediated expansion/activation of T cells within the tumors.

Additional pre-clinical data generated by Carisma has shown the potential additive benefit of CAR-M in combination with PD-1 blockade in solid tumor models that are resistant to anti-PD-1 monotherapy.

The landmark CT-0508 clinical trial remains open for enrollment and the U.S. Food and Drug Administration recently granted Fast Track designation to CT-0508 for the treatment of patients with solid tumors. The clinical study evaluating CAR-M in combination with KEYTRUDA (pembrolizumab) is expected to launch in 2022.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

On December 6, 2021 Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported the presentation of interim clinical data from the company’s ongoing Phase 1/2 study of BDC-1001, the company’s lead immune-stimulating antibody conjugate (ISAC) in a poster session at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress 2021, being held virtually from Dec. 6-11, 2021 (Press release, Bolt Biotherapeutics, DEC 6, 2021, View Source [SID1234596478]). The lead author for the poster is Manish Sharma, M.D., START Midwest, with contributions from Ecaterina Dumbrava, M.D., MD Anderson Cancer Center, and other colleagues from the U.S. and South Korea.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The company reported data from 57 subjects participating in an ongoing Phase 1/2 study of BDC-1001, across 16 different types of HER2-expressing solid tumors. BDC-1001 demonstrated a favorable safety and tolerability profile at all evaluated doses and schedules, showing early signs of clinical activity with corresponding biomarker changes in the tumor microenvironment of post-treatment tumor biopsies. BDC-1001 is an immune-stimulating antibody conjugate (ISAC) comprising a HER2-targeting biosimilar of trastuzumab conjugated with a non-cleavable linker to an innovative TLR7/8 agonist.

"The favorable safety profile and early indications of clinical disease control in the BDC-1001 study are encouraging," said Dr. Sharma, Associate Director of Clinical Research at START Midwest. "There is a clear need for well tolerated, durable treatments in the fight against cancer and I’m excited to see if BDC-1001 can deliver on that potential as we explore higher drug exposure levels."

The poster presentation at ESMO (Free ESMO Whitepaper) I-O reported new safety, pharmacokinetic/pharmacodynamic, and efficacy results for the ongoing Phase 1 dose-escalation portion of the BDC-1001 monotherapy trial. Fifty-seven subjects have been treated at increasing dose levels up to 20 mg/kg every three weeks and 12 mg/kg every two weeks, and data from these subjects demonstrate that:

BDC-1001 continues to have a favorable safety and tolerability profile with mild (grade 1/grade 2) infusion related reactions in some patients and no dose-limiting toxicities at dose levels up to 20 mg/kg every three weeks and 12 mg/kg every two weeks. There was no indication of cytokine release syndrome (CRS), and a maximum tolerated dose (MTD) has not been reached.

Early signs of clinical activity are noted in 13 of 40 tumor evaluable subjects with one durable partial response maintained through 52 weeks and multiple subjects achieving stable disease for >12 weeks.

The pharmacokinetic (PK) data demonstrate increasing peak drug levels with increasing dose, and linearity of PK above the 5 mg/kg dose level. Clinical PK modeling predicts that target exposure levels can be achieved with weekly dosing.

Plasma and tissue biomarker results show increase in multiple biomarkers indicative of myeloid cell and TLR 7/8 activation that is consistent with BDC-1001’s mechanism of action. Increasing drug exposure correlates with increases in plasma cytokines and corresponding biomarker changes in the tumor microenvironment of multiple post-treatment tumor biopsies, with intriguing signs of clinical disease control.

These encouraging data point to the need for increased drug exposure to optimize clinical benefit. The favorable safety profile of BDC-1001 allows for continued enrollment in the dose escalation portion of the study, and the Company’s refined PK model based on data from more than 50 patients predicts that weekly administration will provide BDC-1001 exposures at or above the target exposure threshold. The data also support initiation of the combination therapy study with nivolumab (PD-1 inhibitor).

"Bolt Biotherapeutics is committed to agile clinical development based on data. In this Phase 1/2 study of BDC-1001, we have gained tremendous insight into the ability of this novel candidate to mobilize the patient’s immune system in targeting the tumor and its microenvironment. The increases in myeloid cell infiltration and repolarization of macrophages we’ve seen in multiple post-treatment biopsies are provocative and consistent with our proposed mechanism of action," said Edith Perez, M.D., Chief Medical Officer of Bolt Biotherapeutics. "We look forward to exploring weekly dosing as we get closer to determining the recommended Phase 2 dose for BDC-1001 as monotherapy, and to initiating combination therapy with a checkpoint inhibitor."

Presentation Details

Title: Preliminary results from a phase 1/2 study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors

Lead author: Manish R. Sharma, M.D.

Presentation Number: 164P

Timing: On-demand access beginning Dec. 6 at 12:00 p.m. CET.

The poster presentation will be available on the ESMO (Free ESMO Whitepaper) I-O conference website and on Bolt’s website.

Conference Call and Webcast Details

Bolt Biotherapeutics management will host a conference call for the investment community, in conjunction with the now virtual ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021, to discuss emerging clinical data and insights from the ongoing Phase 1/2 study today, Monday, December 6, 2021, at 8:00 a.m. ET/5 a.m. PT.

The conference call can be accessed by dialing +1 (833) 665-0609 within the U.S. or Canada or by dialing +1 (929) 517-0400 from international locations. The passcode for the call is 2633068. A live webcast, including slides, will be available on the Events & Presentations page of Bolt Biotherapeutic’s website at www.boltbio.com. An archived replay can be accessed for 30 days following the webcast.

About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform

ISACs are a new category of immunotherapy that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs comprise three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, with the goal of durable responses for patients with cancer.