On March 29, 2022 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported pipeline and business progress and fourth quarter and full year 2021 financial results (Press release, Nuvalent, MAR 29, 2022, View Source [SID1234611091]).

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As part of today’s update, Nuvalent is announcing that its Investigational New Drug (IND) application for NVL-655 for the treatment of ALK-positive NSCLC and other solid tumors was cleared by the U.S. Food and Drug Administration (FDA). NVL-655 is a novel ALK-selective inhibitor designed with the aim to address the clinical challenges of emergent treatment resistance, central nervous system (CNS)-related adverse events, and brain metastases that may limit the use of currently available ALK inhibitors. Nuvalent plans to initiate the ALKOVE-1 Phase 1/2 study of NVL-655 for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors in the second quarter of 2022.

"The Nuvalent team has continued to demonstrate the ability to discover novel molecules with preclinical profiles suggesting best-in-class potential and to progress them efficiently into clinical development. With the clearance of our IND for NVL-655, Nuvalent is on track to have two parallel lead compounds in clinical trials by mid-year," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We believe we are well positioned with two clinical-stage, novel product candidates in areas of significant medical need, and sustainable internal discovery efforts with the goal of delivering multiple additional product candidates. I am incredibly proud of all that this team has accomplished and their continued dedication to advancing new potential therapeutic options for patients in need."

Recent Pipeline Highlights

Enrollment Ongoing in ARROS-1 Trial of NVL-520 for Patients with Advanced ROS1-positive NSCLC: Nuvalent is actively enrolling patients in the Phase 1 portion of its ARROS-1 clinical trial, a Phase 1/2 study evaluating NVL-520 in patients with advanced ROS1-positive NSCLC and other solid tumors. NVL-520, Nuvalent’s lead product candidate, is a novel ROS1-selective inhibitor designed with the aim to address the clinical challenges of emergent treatment resistance, CNS adverse events, and brain metastases that may limit the use of currently available ROS1 kinase inhibitors.
Discovery Pipeline Advancing toward Selection of Next Development Candidates: Nuvalent continues to advance its early pipeline efforts with multiple discovery-stage research programs. The company expects to nominate product candidates in 2022 for its discovery programs directed toward ALK IXDN compound resistance mutations and HER2 exon 20 insertions.
Recent Business Highlights

Strengthened Board of Directors with Appointment of Emily Drabant Conley, Ph.D.: In February 2022, Nuvalent appointed Emily Drabant Conley, Ph.D., Chief Executive Officer of Federation Bio, to its Board of Directors. Dr. Conley’s work has contributed to industry-shaping advances in genomics that empower patients and clinicians with actionable health data. Prior to Federation Bio, she spent over a decade at 23andMe where, as Vice President of Business Development, she was instrumental in powering the company’s growth from 30 employees into a household name.
Fourth Quarter and Full Year 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $288.1 million as of December 31, 2021. Nuvalent expects that its existing cash, cash equivalents and marketable securities will be sufficient to fund its planned operations into 2024.
R&D Expenses: Research and development (R&D) expenses were $13.2 million for the quarter ended December 31, 2021, and $35.6 million for the year ended December 31, 2021.
G&A Expenses: General and administrative (G&A) expenses were $4.2 million for the quarter ended December 31, 2021, and $10.3 million for the year ended December 31, 2021.
Net Loss: Net loss was $17.3 million for the quarter ended December 31, 2021, and $46.3 million for the year ended December 31, 2021.

On March 29, 2022 Monte Rosa Therapeutics, Inc. (NASDAQ: GLUE), a biotechnology company developing novel molecular glue degrader (MGD) medicines, reported business highlights and financial results for the fourth quarter and full year, ended December 31, 2021 (Press release, Monte Rosa Therapeutics, MAR 29, 2022, View Source [SID1234611090]).

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"Last year was transformational for Monte Rosa as we continued to build our world-class leadership team, expanded operations across our two sites in Boston and Basel, named MRT-2359 – our development candidate for the GSPT1 program – and secured $377.6 million in funding," said Markus Warmuth, M.D., CEO of Monte Rosa. "As we look to 2022, we anticipate significant pipeline progress, including the submission of our IND for MRT-2359, as well as continued lead optimization on our CDK2 and NEK7 programs. We are also seeing exciting advancements across our proprietary QuEEN platform, including the expansion of our understanding of structural characteristics of degradable proteins driven by both our experimental and AI platforms. We believe we are well-positioned both organizationally and financially to execute on our vision of tackling historically undruggable targets and identifying potent, highly selective therapies for patients with few or no treatment options."

FOURTH QUARTER 2021 & RECENT HIGHLIGHTS

•Presented preclinical data for MRT-2359 demonstrating anti-tumor activity in L- and N-Myc-positive non-small cell lung cancer patient-derived xenograft (PDX) models. The data were featured as part of the company’s presentation at the 40th Annual J.P. Morgan Healthcare Conference. MRT-2359 is a potent, selective and orally bioavailable GSPT1-directed molecular glue degrader. MRT-2359 has been shown to induce tumor regression in multiple Myc-driven preclinical models, including models of non-small cell lung cancer and small cell lung cancer

•Advanced CDK2 degrader program into lead optimization. Leveraging the company’s QuEEN platform, Monte Rosa has identified selective MGDs for CDK2, a highly validated oncogenic driver of breast, gynecological and other cancers

•Announced license and research collaboration agreement with Dr. Nir London and the Yeda Research and Development Company Ltd., the commercial arm of the Weizmann Institute of Science. The goal of the collaboration is to leverage innovative covalent chemistry to further expand the target space for molecular glue degradation

•Strengthened executive leadership team with promotions of Jullian Jones, Ph.D., J.D., MBA, to Chief Business Officer and Phil Nickson, Ph.D., J.D., to General Counsel

•Presented at recent scientific and medical conferences, including:
•3rd Annual Protein Degradation and Targeting Undruggables Congress, March 8-9
•ESMO Targeted Anticancer Therapies Congress 2022, March 7-8
•2nd Annual Targeted Protein Degradation Europe, March 15-17

UPCOMING MILESTONES & DATA PRESENTATIONS

•Submission of Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for MRT-2359 expected in mid-2022

•Initiation of at least one additional lead optimization program expected in 2022

•Share new preclinical data supporting MRT-2359 program in a poster presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, hosted April 8-13, 2022, in New Orleans; presentation details, as follows:
Title: Identification of MRT-2359 a potent, selective and orally bioavailable GSPT1-directed molecular glue degrader (MGD) for the treatment of cancers with Myc-induced translational addiction

Abstract: 3929

Presenter: Gerald Gavory, Ph.D.

Date and Time: April 13, 2022, 9:00 AM – 12:30 PM

UPCOMING INVESTOR EVENTS

Monte Rosa will be participating in the following upcoming investor conferences:

•Wells Fargo Biotech Forum, April 11-13
•Piper Sandler Boston Biotech Bus Tour, May 4-5
•UBS Global Healthcare Conference, May 23-25
•Jefferies Global Healthcare Conference, June 8-10

FOURTH QUARTER AND FULL YEAR 2021 FINANCIAL RESULTS

Research and Development (R&D) Expenses: R&D expenses were $18.1 million for the fourth quarter of 2021 and $57.2 million for the year ended December 31, 2021, compared to $9.9 million and $24.0 million, respectively for the same periods of 2020. These increases were due to the expansion of research and development activities, including the development of our QuEEN

ACTIVE/115879056.5

platform and discovery, lead optimization efforts of our GSPT1 program, and the advancement of development candidate MRT-2359, as well as increases in headcount and laboratory-related expenses due to our continued growth as a research and development organization. R&D expenses included non-cash stock-based compensation of $1.0 million for the fourth quarter of 2021 and $2.6 million for the year ended December 31, 2021, compared to $0.1 million and $0.2 million, respectively, for the same periods in 2020.

General and Administrative (G&A) Expenses: G&A expenses for the fourth quarter of 2021 were $5.3 million compared to $2.1 million for the fourth quarter of 2020, and $15.7 million for the year ended December 31, 2021, compared to $4.0 million for the year ended December 31, 2020. The increase in G&A expenses were a result of increased headcount and expenses in support of the company’s growth and operations as a public company and director and officer liability insurance. G&A expenses included non-cash stock-based compensation of $1.0 million for the fourth quarter of 2021 and $2.6 million for the year ended December 31, 2021, compared to $0.1 million and $0.2 million, respectively, for the same periods in 2020.

Net Loss: Net loss for the fourth quarter of 2021 was $23.4 million compared to $19.7 million for the fourth quarter of 2020, and $74.0 million for the year ended December 31, 2021, compared to $35.9 million for the year ended December 21, 2020.

Cash Position and Financial Guidance: Cash, cash equivalents and restricted cash as of December 31, 2021, were $351.4 million, compared to $42.9 million as of December 31, 2020. The company expects that its cash and cash equivalents, including the aggregate net proceeds from the initial public offering, will be sufficient to fund planned operations and capital expenditures into late 2024.

On March 29, 2022 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing IgM antibodies, reported its financial results for the fourth quarter and full year ended December 31, 2021 and provided an update on recent developments (Press release, IGM Biosciences, MAR 29, 2022, View Source [SID1234611089]).

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"IGM continues to make progress in creating a new class of antibody medicines, which strengthens our commitment to use our expertise to develop and improve upon the inherent qualities of IgM antibodies," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "Notably, our exclusive collaboration agreement with Sanofi, announced today, will accelerate the development of our IgM antibody platform across multiple areas of high unmet need beyond our current pipeline efforts. This partnership is a significant step towards exploring and validating our platform in multiple therapeutic areas, and we look forward to working with Sanofi’s impressive team. Simultaneously, our pipeline continues to progress with considerable speed. Namely, the initiation of two Phase 2 studies for our T cell bispecific antibody IGM-2323 and the continued progress in our DR5 agonist IGM-8444 Phase 1 combination treatment regimens. We look forward to sharing information on these efforts later this year."

Global R&D Collaboration with Sanofi

An exclusive worldwide collaboration agreement with Sanofi for multiple oncology, autoimmune and inflammation targets was announced.
IGM and Sanofi will leverage IGM’s proprietary IgM antibody technology platform to discover IgM antibody agonists against three oncology targets and three autoimmune/inflammation targets.
IGM will receive a $150 million upfront payment and potentially over $6 billion in aggregate development, regulatory and commercial milestones. A 50:50 profit share in certain major market countries and tiered royalties in the rest of world is planned for oncology targets, and IGM will receive tiered royalties for autoimmune/inflammation targets. Sanofi has also expressed an interest in purchasing up to $100 million of IGM non-voting common stock in a public financing.
Closing of the collaboration is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 in the U.S., and other customary closing conditions.
Pipeline Updates

IGM-2323 (CD20 x CD3)

Phase 2 studies initiated. IGM announced the initiation of two Phase 2 studies to assess the safety and efficacy of two doses of IGM-2323, 100 mg and 300 mg, in patients with diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). If supportive, the data from this Phase 2 multicenter, open-label study could potentially be used as the basis for accelerated review and approval of IGM-2323.
Presented Phase 1 clinical results: In December 2021, IGM presented clinical results from its Phase 1 trial evaluating IGM-2323 at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The data was featured in an oral presentation titled "A Phase 1 Dose Escalation Study of IGM-2323, a Novel Anti-CD20 x Anti-CD3 IgM T Cell Engager (TCE) in Patients with Advanced B-Cell Malignancies".
IGM-8444 (DR5)

Clinical development of IGM-8444 advances. IGM continues to advance the clinical development of IGM-8444, the Company’s IgM DR5 agonist, in an open-label, multicenter, Phase I study of IGM-8444 as a single agent and in combination in subjects with relapsed and/or refractory solid and hematologic cancers. IGM expects to report initial monotherapy and combination data in solid tumors from the dose escalation portion of this Phase 1 trial in 2022.
Third FOLFIRI dose cohort successfully completed. IGM announced that it has cleared the third of four planned FOLFIRI combination dose escalation cohorts (3.0 mg/kg Q2W) with no dose limiting toxicities (DLTs) and no clinically significant liver toxicity observed to date. IGM is currently enrolling patients in the final planned FOLFIRI combination dose escalation cohort (10.0 mg/kg Q2W).
First birinapant dose cohort successfully completed. IGM also announced that it has cleared the first of four planned birinapant combination dose escalation cohorts with no DLTs and no clinically significant liver toxicity observed to date. IGM is currently enrolling patients in the second planned birinapant combination dose escalation cohort.
IGM-7354 (IL-15 x PD-L1)

IND filing expected in 2022. IGM expects to file an Investigational New Drug Application (IND) for IGM-7354, the Company’s IL-15 x PD-L1 bispecific IgM antibody, in solid tumors in 2022.
IGM-2644 (CD38 x CD3)

IND filing expected in 2022. IGM expects to file an IND for IGM-2644, the Company’s CD38 x CD3 bispecific IgM antibody, in multiple myeloma in 2022.
Corporate Updates

Announced grant agreement with the Bill & Melinda Gates Foundation. The agreement aims to leverage IGM’s engineered IgM and IgA antibodies for the potential prevention of malaria, a significant driver of morbidity and mortality in low- and middle-income countries.

Carrie Brodmerkel, Ph.D., appointed Chief Scientific Officer of IGM Autoimmunity and Inflammation. Dr. Brodmerkel brings extensive experience across a broad range of disciplines to this role. Most recently, she served as Vice President and Global Head of Exploratory Biology and Scientific Strategy at Janssen R&D, a division of Johnson & Johnson, where she was responsible for scientific and strategic leadership of the biotherapeutics portfolio, functional planning and execution, computational sciences, and exploratory biology across therapeutic areas including immunology, hematology, and oncology.
Fourth Quarter and Full Year 2021 Financial Results

Cash and Investments: Cash and investments as of December 31, 2021 were $229.5 million, compared to $366.3 million as of December 31, 2020.
Research and Development (R&D) Expenses: For the fourth quarter and year ended 2021, R&D expenses were $39.2 million and $127.0 million, respectively, compared to $19.6 million and $65.0 million for the fourth quarter and year ended 2020, respectively.
General and Administrative (G&A) Expenses: For the fourth quarter and year ended 2021, G&A expenses were $11.5 million and $38.3 million, respectively, compared to $5.1 million and $18.3 million for the fourth quarter and year ended 2020, respectively.
Net Loss: For the fourth quarter of 2021, net loss was $50.6 million, or a loss of $1.50 per share, compared to a net loss of $24.6 million, or a loss of $0.79 per share, for the fourth quarter of 2020. For the year ended 2021, net loss was $165.2 million, or a loss of $4.93 per share, compared to a net loss of $81.4 million, or a loss of $2.65 per share, for the year ended 2020.
2022 Financial Guidance:
IGM expects full year GAAP operating expenses of $250 million to $260 million including estimated non-cash stock-based compensation expense of approximately $50 million. Concurrent with the Company’s first quarter 2022 financial results expected in May, IGM anticipates providing full year collaboration and license revenue guidance as well as ending 2022 cash and investments guidance.

Conference Call and Webcast
IGM will host a conference call and webcast to discuss the Sanofi R&D collaboration announcement today, March 29, at 8:00 a.m. ET. The conference call may be accessed by dialing (866) 649-1996 (domestic) or (409) 217-8769 (international) and referring to conference ID 4983742. A live webcast of the presentation will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days following the presentation.

On March 29, 2022 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported that the Company will host a conference call and live audio webcast today, Tuesday, March 29, 2022, at 8:00 am ET to discuss the Company’s global collaboration agreement with Sanofi, as recently announced (Press release, IGM Biosciences, MAR 29, 2022, https://investor.igmbio.com/news-releases/news-release-details/igm-biosciences-host-conference-call-and-webcast-today-discuss [SID1234611088]).

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The conference call may be accessed by dialing (866) 649-1996 (domestic) or (409) 217-8769 (international) and referring to conference ID 4983742. A live webcast of the presentation will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days following the presentation.

On March 29, 2022 Sanofi (NASDAQ: SNY) and IGM Biosciences, Inc. (Nasdaq: IGMS) reported the signing of an exclusive worldwide collaboration agreement to create, develop, manufacture, and commercialize IgM antibody agonists against three oncology targets and three immunology/inflammation targets (Press release, IGM Biosciences, MAR 29, 2022, View Source [SID1234611087]). Engineered IgM antibodies represent a new class of potential therapeutics that combine the multi-valency of IgM antibodies possessing 10 binding sites compared to conventional IgG antibodies having only 2 target binding sites.

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John Reed, M.D., Ph.D.
Global Head of Research and Development, Sanofi

"We look forward to this collaboration with IGM Biosciences, a pioneer in a new class of antibody medicines for the treatment of cancer, immunology, and inflammatory diseases. The IGM Biosciences technology platform offers an exciting approach to developing high-avidity IgM antibodies that can efficiently bind and stimulate the activity of cell surface receptors. This unique platform has the potential to overcome historical limitations of conventional IgG antibodies when seeking agonists of some classes of receptors."

Fred Schwarzer
Chief Executive Officer of IGM Biosciences

"Sanofi is a global leader in the development and commercialization of innovative therapies, and we welcome the addition of their extensive expertise and resources in expanding and accelerating the development of our IgM antibody platform across multiple areas of high unmet need.

This partnership builds on an existing research collaboration with Sanofi and is a key step towards our goal of unlocking the full breadth of potential for this important new class of therapeutics. We are pleased to share this vision with Sanofi and look forward to working together on these six potentially first- and best-in-class programs."

Terms of the Collaboration
Under the terms of the agreement, IGM will receive a $ 150 million upfront payment. Sanofi has also expressed an interest in purchasing up to $100M of IGM non-voting common stock in a public financing.

For each oncology target collaboration program, IGM will lead research and development activities, and assume related costs, through approval of the first biologics license application (BLA) for a product directed to that oncology target by the FDA or EMA in exchange for up to $940 million in development and regulatory milestones per oncology target. After receipt of the first marketing approval for a product directed to an oncology target, Sanofi will lead all subsequent development and commercialization activities for that oncology target. For each oncology target, the companies will share profits 50:50 in certain major markets, and IGM will be eligible to receive tiered royalties on net sales in the rest of world.

For each immunology/inflammation target collaboration program, IGM will lead research and development activities, and assume related costs, through the completion of Phase 1 clinical trial for up to two constructs directed to each immunology/inflammation target, after which Sanofi will be responsible for all future development and related costs, in exchange for up to $1,065 million in aggregate development and regulatory and commercial milestones per immunology/inflammation target. Following the completion of Phase 1 clinical trial for each immunology/inflammation target, Sanofi will be responsible for subsequent development activities, commercialization efforts, and related costs. IGM is eligible to receive tiered high single-digit to low-teen royalties on global net sales.

Closing of the collaboration is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 in the U.S., and customary closing conditions.