On September 16, 2021 Boehringer Ingelheim reported a clinical phase I collaboration with Amgen to evaluate the combination of BI 1701963, the first and most advanced SOS1::pan-KRAS inhibitor exhibiting activity against a broad spectrum of KRAS alleles, and LUMAKRAS (sotorasib), the first US Food and Drug Administration (FDA) approved KRASG12C inhibitor for adult patients with locally advanced or metastatic non-small cell lung cancer (Press release, Boehringer Ingelheim, SEP 16, 2021, View Source [SID1234587821]). The trial will investigate potential synergistic effects of this combination, possibly improving therapeutic outcomes beyond those of KRASG12C inhibitor therapy alone, specifically for people living with lung and colorectal cancers.

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Preclinical data suggest that the combination of a KRASG12C inhibitor with a SOS1::pan-KRAS inhibitor may result in increased anti-tumor activity in KRAS G12C-driven cancers based on the complementary mechanisms of these targeted oncology agents.1,2 By shifting the equilibrium from active KRAS towards the inactive form, SOS1::pan-KRAS inhibitors have the potential to sensitize KRAS G12C-mutant tumors to covalent KRASG12C inhibitors that bind to inactive KRAS. In addition, SOS1 inhibitors block feedback reactivation which occurs upon pathway inhibition.

"We are excited to partner with Amgen, who have pioneered KRAS G12C inhibition, and to further expand our program to make a difference for people living with KRAS-driven cancers," said Francesco Di Marco, Ph.D., Corporate Senior Vice President, Global Therapy Area Head Oncology at Boehringer Ingelheim. "Boehringer Ingelheim follows an ‘all-in’ research approach to taking cancer on, including the first and most advanced SOS1::pan-KRAS inhibitor which we investigate in several combinations and cancer types to realize even more opportunities to deliver potential therapeutic benefits to cancer patients."

Under the terms of the non-exclusive collaboration, Amgen will be the sponsor of the trial and Boehringer Ingelheim and Amgen will jointly share the costs of and oversee clinical development for the combined therapy.

About BI 1701963
BI 1701963 is an investigational, orally available small molecule, that binds to the catalytic domain of SOS1 preventing the interaction with inactive KRAS. This reduces the formation of active KRAS and in consequence inhibits MAPK pathway signaling in KRAS-dependent cancers. SOS1 inhibition also simultaneously blocks feedback driven reactivation of the MAPK pathway. The selective inhibition of SOS1 is a therapeutic concept that could allow KRAS blockade irrespective of KRAS mutation type (pan-KRAS approach). SOS1::KRAS inhibitors exhibit activity on a broad spectrum of KRAS alleles, including all major G12D/V/C and G13D oncoproteins, as published by Hofmann MH, et al. in Cancer Discovery, a journal of the American Association of Cancer Research (AACR) (Free AACR Whitepaper). BI 1701963 is currently being evaluated in phase I clinical trials in patients with advanced KRAS-mutated cancers to evaluate safety, tolerability, pharmacokinetic and pharmacodynamic properties, and preliminary efficacy of BI 1701963 alone and in combination with MEK inhibitors, KRASG12C inhibitors or irinotecan.

On September 16, 2021 Xilio Therapeutics, Inc. (Xilio) a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported that the first patient has been dosed in the company’s Phase 1/2 clinical trial evaluating XTX101 for the treatment of solid tumors (Press release, Xilio Therapeutics, SEP 16, 2021, View Source [SID1234587839]). XTX101 is a tumor-selective anti-CTLA-4 monoclonal antibody designed to improve upon the therapeutic index of existing anti-CTLA-4 therapies by overcoming their historical potency and tolerability limitations.

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"The initiation of our first clinical trial with XTX101 is an exciting moment for Xilio and for the patients with cancer who we believe would benefit from anti-CTLA-4 therapies, but are limited because of toxicity challenges," said Marty Huber, M.D., chief medical officer of Xilio Therapeutics. "In preclinical studies, XTX101 has shown potential to deliver meaningful responses and favorable tolerability. Our Phase 1/2 clinical trial will evaluate XTX101 as a monotherapy as well as in combination with the checkpoint inhibitor pembrolizumab. We look forward to advancing this trial and exploring the therapeutic potential of XTX101 for patients."

Leveraging its proprietary geographically precise solutions (GPS) platform, Xilio engineered XTX101 to be activated in the tumor microenvironment with the potential to result in localized clinical activity without dose-limiting toxicities. In preclinical studies, XTX101 exhibited tumor-selective biological activity and robust tumor growth inhibition, including complete responses in murine cancer models, with favorable tolerability. These data demonstrate enhanced activity and an improved tolerability profile compared to an analog of ipilimumab, a CTLA-4 blocking antibody approved for the treatment of certain solid tumor cancers. XTX101 has also demonstrated enhanced tumor growth inhibition and tolerability when administered in combination with an anti-PD-1 in vivo.

The Phase 1/2 clinical trial is a first-in-human, multi-center, open-label trial that will evaluate the safety and tolerability of XTX101 as a monotherapy, as well as a combination therapy with pembrolizumab, for the treatment of adult patients with advanced solid tumors. The Phase 1 portion of the trial will consist of three cohorts, beginning with an accelerated and standard 3+3 dose-escalation monotherapy cohort to assess the tolerability of XTX101 at the target dose in patients with advanced solid tumors who have progressed after receiving the standard-of-care treatment for their tumor. Following completion of enrollment in the dose-escalation cohort, XTX101 will be evaluated in a monotherapy cohort designed to evaluate evidence of anti-CTLA-4 pharmacodynamic activity in patients who have progressed on anti-PD-1 or anti-PD-L1 treatment but have not received prior treatment with an anti-CTLA-4 therapy, and XTX101 will be evaluated in combination with pembrolizumab in patients who have not previously been treated with an anti-PD-1 or anti-PD-L1 treatment. The Phase 1 portion of the trial is anticipated to enroll approximately 100 patients across all cohorts at multiple sites in the United States.

On September 16, 2021 Bantam Pharmaceutical, a drug discovery and development company targeting selective modulation of mitochondrial dynamics in cancer, reported that it has completed a $25 million Seed Funding to finalize its ongoing IND-enabling activities for its lead program, BTM-3566, and consummate preparations for first in human clinical trials (Press release, Bantam Pharmaceutical, SEP 16, 2021, View Source [SID1234587854]). The funding was co-led by Bantam’s current investors.

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Bantam plans to submit its Investigational New Drug application in February 2022 and start Phase 1 clinical studies in patients with B-cell hematological malignancies in the second quarter of 2022. In addition, Bantam has established its operations in the Alexandria cluster based in Research Triangle Park, an area rich in clinical development resources and capabilities.

"This funding enables Bantam Pharmaceutical to be fully prepared to enter the clinic for first in human studies in early 2022, representing a major milestone. We are excited about moving to the next stage of development," said Lionel Goldfrank, Co-founding investor and board member.

BTM-3566 is a novel selective modulator of mitochondrial dynamics, targeting a pathway involved in mitochondrial homeostasis that specifically drives cancer cell apoptosis in a number of tumor types with high unmet need. The company has leveraged a protein translational phenotypic screen to discover its clinical candidate and related compounds.

"This Fall we will raise our Series A round to drive clinical development studies and expand our discovery platform to accelerate our novel drug programs and address the ongoing unmet needs of many different cancers, beginning with B-cell hematological malignancies," said Michael Stocum, President and Chief Executive Officer of Bantam. "Our team remains focused on progressing our fundamental scientific insights along the clinical pathway to transform the treatment of patients with cancer."

About BTM-3566
BTM-3566 is a novel selective modulator of mitochondrial dynamics, targeting a pathway involved in mitochondrial homeostasis that specifically drives cancer cell apoptosis. Bantam has leveraged a protein translational phenotypic drug discovery and precision medicine-based platform approach to identify the pathway and related biomarkers, enabling enrichment of patient populations most likely to respond to BTM-3566. Initial clinical proof of concept will focus on areas of unmet clinical need with initial phase I/II clinical trials planned in relapsed/refractory B-cell hematological malignancies, including Diffuse Large B-cell Lymphoma.

On September 16, 2021 Endeavor BioMedicines, a clinical-stage precision medicine company targeting the core drivers of multiple terminal diseases including oncology and fibrosis, reported the in-licensing of a ULK1/2 inhibitor program from the Salk Institute for Biological Studies and Sanford Burnham Prebys (Press release, Endeavor BioMedicines, SEP 16, 2021, View Source [SID1234606754]). The license agreement provides Endeavor with exclusive worldwide rights to ENV-201, an orally available small molecule inhibitor of ULK1/2, a critical enzyme in a cellular recycling process called autophagy that is often linked to drug resistance in RAS- and LKB1-mutated cancers. Endeavor plans to complete IND-enabling studies and advance the program into the clinic initially in colorectal and lung cancers in the next 18 months.

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"The Salk Institute and Sanford Burnham Prebys have pioneered early research on the ULK1/2 pathway in RAS-mutated cancers, including those that have become resistant to current standard of care," said John Hood, Ph.D., Co-Founder, CEO and Chairman of Endeavor. "This powerful ULK1/2 program that we have acquired is synergistic with our growing portfolio of precision medicine treatments and has the potential to be an important new treatment option for patients with life-threatening colorectal and lung cancers."

Mutations in the tumor suppressor LKB1 are found in approximately 15% of all people with non-small cell lung cancer and a significant number of individuals with other cancers, including colorectal carcinoma. LKB1 mutations remove a "brake" preventing oncogenesis and are frequently co-mutated with KRAS oncogenes which stimulates oncogenesis. These patients are generally resistant to the standard of care (chemotherapy or immuno-oncology treatment) and face a very poor prognosis. In preclinical models, the ULK1/2 inhibitor ENV-201 demonstrated single-agent activity against these tumors providing a potential therapeutic option where there is none today. Endeavor intends to advance the orally available, small molecule compound as a single-agent treatment, and the company also plans to explore combination treatment with cancer immunotherapy in refractory patients.

"Since we initially discovered how cancer cells starved of nutrients activate ULK1/2, we focused on finding a drug that could block its activity," said Nicholas Cosford, Ph.D., professor and deputy director of the NCI-designated Cancer Center at Sanford Burnham Prebys. "Using medicinal chemistry, chemical biology and rational drug design, we created compounds that inhibit ULK1/2 and we are hopeful this approach will have an impact as an anti-cancer treatment. This agreement with Endeavor BioMedicines moves our efforts closer to our goal of helping people living with cancer."

"We are excited that Endeavor BioMedicines will be advancing the ULK1/2 program into clinical development – a program that has the potential to be an extraordinary therapeutic option for patients who have certain genetically defined, life-threatening cancers," said Reuben Shaw, Ph.D., professor, Molecular and Cell Biology Laboratory, William R. Brody Chair, Salk Institute for Biological Studies. "It is the right time to pass the baton to Endeavor for late preclinical and clinical development, and it underscores the strength of San Diego’s biotech ecosystem for the benefit of patients who have significant unmet medical need."

Targeting a Cellular Recycling Progress in Cancer Biology

The laboratories of Shaw and Cosford collaborated to develop a portfolio of small molecule inhibitors of ULK1/2, a critical enzyme in a cellular recycling process called autophagy. Tumor cells use this cellular recycling process to supply much-needed nutrients and metabolites when there are not enough nutrients in the available blood supply. Tumors with high levels of autophagy are resistant to standard therapies and those patients generally have a very poor prognosis. Researchers have also found that specific genetic mutations frequently found in lung, colorectal and pancreatic cancer make those tumors highly dependent on this recycling pathway. The combined research suggests that drugs targeting ULK1/2 to inhibit autophagy should work well in genetically defined cancers alone or in combination with existing chemo-, targeted- and immuno-therapeutics.

On September 16, 2021 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies and vaccines, reported a $55.0 million private investment in public equity (PIPE) financing from the sale of 5,000,000 shares of its common stock at a price per share of $11.00 (Press release, Gritstone Oncology, SEP 16, 2021, View Source [SID1234592013]). Gross proceeds from the PIPE financings total $55.0 million, before deducting placement agent fees and offering expenses. The PIPE is being led by Frazier Life Sciences Public Fund, with additional participation from Redmile Group and Gilead Sciences.

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"As long-term backers of Gritstone, we continue to be impressed by the company’s progress and emergence as a leader in development of next generation immunotherapies and vaccines for cancer and infectious diseases," said Jamie Brush, M.D., General Partner and Portfolio Manager of the Frazier Life Sciences Public Fund. "We believe Gritstone’s EDGE platform and integrated vaccine manufacturing capabilities uniquely position the company to rapidly expand into infectious disease vaccine development with a potentially refrigerator stable self-amplifying mRNA vaccine platform. This financing will help ensure Gritstone has the resources to move quickly in this exciting new area, and we are excited to support the company in its next phase of growth."

The closing of the PIPE financing is subject to customary closing conditions and is expected to close by September 17, 2021. Cowen served as the sole placement agent for the PIPE financing.

The securities sold in this private placement have not been registered under the Securities Act of 1933, as amended, and may not be offered or sold in the U.S. except pursuant to an effective registration statement or an applicable exemption from the registration requirements. Gritstone bio has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock issued in this private placement.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.