On October 14, 2022 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), a biopharmaceutical company focused on the discovery and development of covalent small molecules to treat patients with genetically defined cancers and metabolic diseases, reported that the U.S. Food and Drug Administration (FDA) has cleared Biomea’s IND application to begin a Phase I/Ib trial of BMF-219, a selective, covalent menin inhibitor in patients with unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC with an activating KRAS mutation (Press release, Biomea Fusion, OCT 14, 2022, View Source [SID1234622021]).

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"We are very excited to open this particular IND as we now look to validate the preclinical potential of BMF-219 in patients across several solid tumor types who have a KRAS mutation, which currently is associated with a very poor survival prognosis," said Thomas Butler, Biomea’s CEO and Chairman of the Board. "In January 2022, we mapped out perhaps one of the more aggressive clinical development plans among peer companies to initiate clinical studies of BMF-219 in up to seven tumor types by the end of 2022. I am so incredibly proud of our team’s extraordinary efforts to deliver on this plan, motivated by the persistent and significant unmet needs of numerous cancer patients."

Mr. Butler continued, "I would like to thank the FDA for their extraordinary effort clearing our IND on-time, and also our contract research organizations, our consultants, our investors, and of course TEAM FUSION for their commitment, guidance, and support in generating another broad and promising IND package for BMF-219."

KRAS is the most frequently mutated isoform amongst RAS oncogenes in human solid tumors, with high prevalence in NSCLC, CRC, and pancreatic cancer. With only one approved therapy targeting KRAS G12C for locally advanced or metastatic NSCLC, KRAS-driven tumors continue to represent a significant unmet medical need. A targeted pan-KRAS inhibitor has the potential to treat 25-35% of NSCLC, 35-45% of CRC, and approximately 90% of PDAC patients.

Menin is a scaffold protein and a required co-factor of oncogenic transcriptional proteins with functional interactions that are critical for the development of various cancers. As previously reported by Biomea Fusion, KRAS-mutant NSCLC, CRC, and PDAC cell lines and ex vivo preclinical models were highly sensitive to BMF-219. In preclinical models, high potency of BMF-219 was observed amongst various KRAS-mutant solid tumor cell lines, but not KRAS wild type, suggesting that BMF-219 broadly inhibited mutant KRAS in these tumor models. As a covalent menin inhibitor, BMF-219 has manifested advantages over the commercially KRAS-targeted inhibitor LUMIKRAS in multiple pre-clinical studies due to the independence of KRAS’ phosphorylation state within G12C tumors, and more broadly the ability to target multiple activating KRAS mutations.

About COVALENT–102
COVALENT-102 is an open-label, multi-cohort, multicenter, Phase I/Ib dose finding study evaluating the safety, tolerability, and clinical activity of escalating doses of oral BMF-219 administered to patients with unresectable, locally advanced, or metastatic NSCLC, CRC, and PDAC with a KRAS mutation.

About Non-Small Cell Lung Cancer (NSCLC)
NSCLC is the most common form of lung cancer, representing approximately 82% of all lung cancer cases or approximately 200,000 cases in the U.S. each year (Source: NCI SEER Data). Additionally, the five-year survival rate of NSCLC is approximately 25%. While lung cancer is the third most common form of cancer in the U.S. based on incidence, it contributes to the highest number of annual cancer deaths in the U.S. KRAS is the most frequently mutated oncogene in NSCLC, occurring in approximately 30% of patients. There remains a great unmet need for targeted therapies to address all KRAS driver mutations and avoid known mechanisms of resistance.

About Colorectal Cancer (CRC)
CRC is the fourth most common form of cancer and the second leading cause of cancer death in the U.S., representing approximately 150,000 cases in the U.S. each year (Source: NCI SEER Data). These cancers start in the rectum or the colon and can be diagnosed/identified early, even potentially as noncancerous polyps. The five-year survival rate of CRC is approximately 65%. Among other mutations, KRAS mutations occur in approximately 40% of patients with CRC. These mutations can not only help predict the absence of response to anti-EGFR therapy, but also result in poorer overall survival. Therefore, there’s a growing unmet need for personalized therapies for patients with KRAS-mutant colorectal cancer.

About Pancreatic Cancer (PDAC)
Pancreatic cancer is a relatively rare form of cancer in the U.S., representing approximately 60,000 cases in the U.S. each year (Source: NCI SEER Data). Pancreatic cancer is an aggressive cancer with a very low five-year survival rate of approximately 11%, indicating that there is a large unmet need. 80% of patients are diagnosed at an advanced stage, contributing to the low survival rate. KRAS mutations are found in nearly all pancreatic cancer patients and are considered as a driver of the malignant process in most of those patients.

On October 14, 2022 Mablink Bioscience ("Mablink"), a biotechnology company aiming to transform cancer therapy using next-generation antibody-drug conjugates (ADCs), reported that it has raised a €31 million Series A funding round to advance its lead candidate to the clinic and to build a pipeline of ADCs using its proprietary platform technology (Press release, Mablink Bioscience, OCT 14, 2022, View Source;utm_medium=rss&utm_campaign=mablink-bioscience-announces-a-e31-million-series-a-funding-round-led-by-sofinnova-partners-and-merieux-equity-partners [SID1234622018]). The round was led by Sofinnova Partners and Mérieux Equity Partners, with participation from the existing investors.

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Mablink’s technology is based on a unique structure of chemical links (called "linkers") placed between an antibody and any chosen cytotoxic molecule to be delivered into tumor cells. The unique structure of those linkers masks the cytotoxic molecule which provides a "stealthy" property to Mablink’s ADCs, conferring two highly desirable pharmacological properties. First, it enables ADCs to stay longer in the body and gives them more time to destroy tumor cells. Second, these stealth ADCs have greatly improved tolerability. These two aspects translate into a 10-fold increase of the therapeutic index observed in animal models, a potentially game-changing factor for future clinical successes in the ADC space.

"We are very proud to be joined by such experienced investors," said Jean-Guillaume Lafay, Chief Executive Officer and co-founder of Mablink. "They bring the necessary funds but also the expertise and network that will be critical for the success of Mablink in bringing its first ADC to the clinic. We are also thankful to our historical investors who decided to reinvest in this round."

The proceeds of this financing round will enable Mablink to become a clinical-stage biotech by bringing its lead candidate, MBK-103, into clinical development for the treatment of solid tumors, notably ovarian cancer. At the same time, Mablink will build a pipeline of ADCs for solid tumors.

"Mablink offers a complete solution that tackles the challenges currently limiting the development of ADCs," said Graziano Seghezzi, Managing Partner at Sofinnova Partners. "With its "masking" technology, we have the potential to build a pipeline of products for patients without real treatment options today. We look forward to working with Jean-Guillaume and his team to transform Mablink into a global ADC player."

Valérie Calenda, Managing Partner of Mérieux Equity Partners, said: "Merieux Equity Partners was attracted by the project at its inception in 2019 and decided to support it through its industrial accelerator M2Care before advising UI Investment and Pertinence Invest 2 to participate to the seed round. Since then, the quality of the team and the progress made reinforced our conviction that this platform can bring to millions of patients safer and more potent ADCs thanks to an improved therapeutic window. We are delighted to continue supporting MabLink by co-leading this Series A financing with our venture fund OMX Europe."

"After a €4M Seed funding a year ago, Mablink enters a new era. We are particularly proud of the success of this Series A funding, which will exponentially increase the capacities and investments of the company in research and development, the consolidation of its pipeline as well as the hiring of seasoned profiles." says Florian Denis, Investment Director at Elaia, for the historic investors.

Dr Calenda and Mr. Seghezzi both join Mablink’s Board of Directors.

Existing shareholders, Elaia Partners, UI-Investissement / Pertinence Invest 2 (advised by Mérieux Equity Partners), Sham Innovation Santé (advised by Turenne Capital), Fondation Fournier-Majoie, Simba Santé (Angelor) and Crédit Agricole Création also participated in the Series A.

On October 13, 2022 NovaRock Biotherapeutics Ltd, a clinical-stage biotechnology company focusing on the development of innovative antibody therapies for cancer and inflammatory diseases reported that Dr. Raymond Yu, Director of Preclinical, will present at the 10th Annual Immuno-Oncology Summit 2022 held in Boston, Massachusetts and on October 12-14, 2022 (Press release, NovaRock Biotherapeutics, OCT 13, 2022, View Source [SID1234623195]). Dr. Yu’s oral presentation highlights our highly potent and safe CD137 Bispecific Antibody Platform for the Development of Solid Tumor Therapeutics.

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Session Category: NOVEL STRUCTURES AND FORMATS
Date: Thursday, October 13, 2022, at 11:30EST

Abstract: First-generation CD137 agonists reached limited clinical outcomes due to hepatotoxicity and/or poor efficacy. With a "fit-for-purpose" design, NovaRock developed a CD137 bispecific platform to activate the co-stimulatory pathway through TAA-mediated receptor clustering. These bispecific antibodies reprogram the tumor microenvironment to elicit potent anti-tumor effects without detectable toxicity and long-lasting immunological memory. Additionally, these antibodies have been optimized to facilitate development and manufacturing. The lead antibody NBL-028 is currently in the IND-enabling stage.

On October 13, 2022 Enliven Therapeutics, Inc. (Enliven), a clinical-stage precision oncology company focused on the discovery and development of next-generation small molecule kinase inhibitors, and Imara Inc. (Nasdaq: IMRA) (Imara) reported that they have entered into a definitive merger agreement to combine the companies in an all-stock transaction (Press release, Enliven Therapeutics, OCT 13, 2022, View Source [SID1234622024]). The combined company will focus on advancing Enliven’s pipeline of precision oncology product candidates. Enliven is advancing two parallel lead product candidates: ELVN-001, a highly selective small molecule BCR-ABL inhibitor designed to address the challenges that limit the efficacy, tolerability and convenience of currently available adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML), and ELVN-002, a potent, selective and irreversible HER2 and pan-HER2 mutant kinase inhibitor for the treatment of HER2 mutant lung cancer and other HER2-driven tumor types. Upon completion of the merger, which is subject to approval by Imara’s and Enliven’s stockholders, the combined company is expected to operate under the name Enliven Therapeutics, Inc. and trade on the Nasdaq Global Select Market under the ticker symbol ELVN.

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In support of the merger, Enliven also intends to raise approximately $165 million in a concurrent private financing co-led by new investors Fairmount and Venrock Healthcare Capital Partners, with participation from additional new investors, which include Fidelity Management & Research Company, RA Capital Management, Frazier Life Sciences and Commodore Capital. All of Enliven’s existing investors will participate in the financing, including OrbiMed, 5AM Ventures, Surveyor Capital (a Citadel company), Cormorant Asset Management, Roche Venture Fund, Sheatree Capital, Boxer Capital, Logos Capital and Janus Henderson Investors. The financing was oversubscribed and new investor allocations account for over 60% of the total size of the financing, which is expected to close immediately prior to the completion of the merger.

With the cash expected from both companies at closing and the proceeds of the planned concurrent financing, the combined company is currently expected to have approximately $300 million of cash and cash equivalents at closing, after transaction expenses. The cash resources are expected to be used to advance Enliven’s pipeline through multiple clinical milestones and provide runway into early 2026. The merger and financing are expected to close in the first quarter of 2023, subject to stockholder approval of both companies, the effectiveness of a registration statement to be filed with the U.S. Securities and Exchange Commission (SEC) to register the shares of Imara common stock to be issued in connection with the merger, and the satisfaction of customary closing conditions.

"We are excited to announce this merger with Imara, which comes at a pivotal moment for Enliven. We recently initiated our Phase 1 clinical trial for ELVN-001, which is being evaluated in adults with CML, and expect to file our IND for ELVN-002 by the end of the year. We expect this transaction to provide Enliven with capital to fund us through multiple key milestones and allow us to explore the potential of our pipeline. We look forward to helping people with cancer to not only live longer, but live better," said Sam Kintz, MBA, Enliven’s Co-founder and Chief Executive Officer.

"Following an extensive and thoughtful review of several strategic alternatives, it became clear that the proposed merger with Enliven was a compelling option for our stockholders," said Rahul Ballal, Ph.D., President and Chief Executive Officer of Imara. "Enliven has a differentiated pipeline, an experienced team and we expect the combined company to be well financed by top-tier investors to execute on its clinical mission. We look forward to the company’s continued progress in the clinic."

About Enliven’s Precision Oncology Portfolio

Enliven is a clinical-stage precision oncology company focused on the discovery and development of potentially best-in-class or first-in-class precision oncology therapies. Enliven’s programs are designed to address issues such as tolerability, combinability, resistance and disease escape through brain metastases. Enliven is advancing two parallel lead product candidates:

ELVN-001: Enliven’s most advanced candidate, ELVN-001, is a potent, highly selective, small molecule kinase inhibitor designed to specifically target the BCR-ABL gene fusion, the oncogenic driver for patients with CML. Although the approval of BCR-ABL TKIs has improved the life expectancy of patients with CML significantly, tolerability, safety, resistance and patient convenience concerns have become more prominent as patients can now expect to live on therapy for decades. These issues can result in the loss of molecular response and disease progression for many patients and drive approximately 20% of patients to switch therapy within the first year and approximately 40% to switch in the first 5 years. Enliven’s preclinical studies showed that ELVN-001 does not meaningfully interfere with the activity of kinases that we believe limit efficacy and tolerability of approved ATP-competitive TKIs. Additionally, given ELVN-001’s mechanism of action, it potentially represents a complementary option to allosteric BCR-ABL inhibitors, which may play an increasingly important role in the standard of care. ELVN-001 was also designed to be efficacious against the T315I mutation, the most common BCR-ABL mutation, which confers resistance to nearly all approved TKIs. Importantly, ELVN-001 was designed to be a more attractive option for patients with comorbidities, on concomitant medications or desiring more freedom from stringent administration requirements. ELVN-001 is currently being evaluated in a Phase 1 clinical trial in adults with CML. To learn more, please visit www.clinicaltrials.gov (NCT05304377).

ELVN-002: Enliven’s second product candidate, ELVN-002, is a potent, selective and irreversible HER2 inhibitor with activity against various HER2 mutations, including Exon 20 insertion mutations (E20IMs) in non-small cell lung cancer (NSCLC), for which there are currently no approved small molecule inhibitors. ELVN-002 is designed to inhibit HER2 and key mutations of HER2, while sparing wild-type EGFR and avoiding EGFR-related toxicities. Enliven believes that if ELVN-002 achieves this profile, it will be able to achieve an improved therapeutic index compared to current approved and investigational TKIs as well as provide a meaningful therapeutic option to patients with brain metastases, a key mechanism of resistance to current therapies in patients with NSCLC and other HER2 driven diseases. While the initial focus for this program is for HER2 mutant NSCLC, Enliven intends to seek to expand the opportunity to patients with other HER2 mutations as well as HER2 amplified tumors including breast, colorectal and gastric cancers.

In addition to its two lead programs, Enliven is pursuing several additional research stage opportunities that align with its development approach. Enliven is in the process of screening and optimizing the chemistry for multiple programs and expects to make a product candidate nomination for its third program in the first half of 2023.

About the Proposed Merger

Under the terms of the merger agreement, Imara will issue to pre-merger Enliven stockholders shares of Imara common stock as merger consideration in exchange for the cancellation of shares of capital stock of Enliven and Enliven will become a wholly-owned subsidiary of Imara. Pre-merger Imara stockholders are expected to own approximately 16% of the combined company and pre-merger Enliven stockholders (including those purchasing Enliven shares in the private financing discussed above) are expected to own approximately 84% of the combined company. The percentage of the combined company that pre-merger Enliven stockholders and pre-merger Imara stockholders will own as of the close of the proposed transaction is subject to certain adjustments as described in the merger agreement, including the amount of Imara’s net cash at closing. Immediately prior to the closing of the proposed merger, pre-merger Imara stockholders will be issued contingent value rights representing the right to receive certain payments received by the combined company, if any, related to the previously announced pending sale of tovinontrine (IMR-687) or related to any potential sale or license of IMR-261.

Upon closing of the proposed transaction, Imara Inc. will be renamed Enliven Therapeutics, Inc. The combined company will be led by Sam Kintz, Co-founder and Chief Executive Officer of Enliven, and other members of the Enliven management team. The combined company’s board of directors will be comprised of all of the directors of Enliven’s board of directors and one director designated from Imara’s board of directors, who is expected to be Rahul Ballal, Imara’s President and Chief Executive Officer.

The merger agreement has been approved by the board of directors of each company and the proposed transaction is expected to close in the first quarter of 2023, subject to approvals by the stockholders of each company, the effectiveness of a registration statement to be filed with the SEC to register the shares of Imara common stock to be issued in connection with the merger, and other customary closing conditions.

Goldman Sachs & Co., LLC, Jeffries and Cowen are serving as financial advisors and placement agents to Enliven. Wilson Sonsini Goodrich & Rosati is serving as legal counsel to Enliven, and Cooley is serving as legal counsel to the placement agents. SVB Securities is serving as the exclusive financial advisor and WilmerHale is serving as legal counsel to Imara.

Conference Call Information

Enliven and Imara will host a conference call today, October 13, 2022, at 5:00 p.m. E.T., to discuss the proposed merger. The conference call may be accessed by dialing (800) 715-9871 (United States and Canada) or (646) 307-1963 (international) and asking to join the Enliven and Imara conference call (conference ID 3259480). A live webcast of the presentation will be available on the Events & Presentations section of Imara’s website at View Source A replay of the webcast will be archived on the Imara website following the presentation.

On October 13, 2022 LianBio, a Princeton-Shanghai company, reported that stopped a Phase III China trial of Truseltiq (infigratinib) following news that Switzerland’s Helsinn Healthcare will stop distributing the liver cancer drug in the US for "business reasons (Press release, LianBio, OCT 13, 2022, View Source [SID1234622020])." The company will request the FDA to withdraw the drug’s approval for cholangiocarcinoma, issued one year ago. Helsinn signed a $2.4 billion partnership deal with BridgeBio of the US to distribute the drug while LianBio acquired greater China rights. LianBio will provide the drug to current China patients and continue a Phase IIa proof-of-concept study of Truseltiq for other indications.

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