On August 8, 2024 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported financial results for the second quarter ended June 30, 2024, and provided a business update (Press release, Altimmune, AUG 8, 2024, View Source [SID1234645641]).

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"During the second quarter, we continued to highlight the scientific evidence supporting the robust therapeutic potential of pemvidutide in metabolic diseases," said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. "The data presented at the European Association for the Study of the Liver (EASL) meeting highlighted the disease-modifying potential of pemvidutide in MASH and reinforces our confidence in achieving success on the MASH resolution and fibrosis improvement endpoints of our Phase 2b IMPACT trial. We also delivered two podium presentations at the American Diabetes Association (ADA) 84th Scientific Sessions that highlighted the robust reductions in body weight and serum lipids with pemvidutide treatment. In addition, we presented data demonstrating class-leading preservation of lean mass among incretin agents, an increasingly important consideration in the treatment of obesity. These data further exemplify the differentiation and broad utility we believe pemvidutide will bring to the rapidly evolving obesity marketplace. We continue to make progress toward expanding the development of pemvidutide in up to three additional indications where its dual GLP-1/glucagon agonism could provide benefit over currently available agents. In parallel with these efforts, our discussions with potential strategic partners continue to progress. We look forward to sharing further updates on each of these initiatives."

Recent Highlights and Anticipated Milestones:

Obesity:

On June 22 and 23, the Company presented data from its Phase 2 MOMENTUM obesity trial at the American Diabetes Association’s (ADA) 84th Annual Scientific Sessions
At 48 weeks of treatment, subjects receiving pemvidutide achieved weight loss of up to 15.6% with weight loss continuing at the end of treatment.
A full analysis of body composition data showed class-leading lean mass preservation among incretin agents with only 21.9% of weight loss attributable to lean mass and 78.1% attributable to fat.
Treatment with pemvidutide also resulted in robust reductions of triglycerides (55.8%), total cholesterol (20.0%) and LDL cholesterol (17.4%) in subjects with elevated baseline lipids on the 2.4mg dose.
In addition, data from the Phase 1 first-in-human trial of pemvidutide demonstrated robust reductions in pro-inflammatory lipids associated with atherogenesis and cardiovascular risk.
End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) expected to take place in late Q3 2024
The Company is seeking agreement from the Agency on the Phase 3 trial design and study endpoints that highlight the differentiation of pemvidutide in the treatment of obesity, including its ability to reduce serum lipids and liver fat content (LFC) and its class-leading preservation of lean mass among incretin agents.
Metabolic Dysfunction-Associated Steatohepatitis (MASH):

On June 5, Altimmune presented data at the EASL International Liver Congress 2024, supporting the disease-modifying potential and differentiated therapeutic profile of pemvidutide in MASH
An analysis of data in our Phase 1 trial of metabolic-associated steatotic liver disease (MASLD) demonstrated that higher proportions of subjects receiving pemvidutide achieved FibroScan-aspartate aminotransferase (FAST) score, MRI-PDFF and alanine aminotransferase (ALT) responses than subjects receiving placebo, suggesting significant rates of MASH resolution and fibrosis improvement may be achieved in the IMPACT Phase 2b MASH trial.
A quantitative systems pharmacology (QSP) computational model predicted that GLP-1/glucagon dual agonism of pemvidutide would have more potent effects on MASH resolution and fibrosis improvement than GLP-1 therapy alone and that both endpoints would be achieved within the 24-week efficacy readout of the IMPACT trial.
Lipidomic profiling showed significant reductions in serum lipids associated with cardiovascular disease, reinforcing our belief in the disease-modifying potential of pemvidutide on MASH-associated cardiovascular co-morbidities.
On July 25, data from the previously reported 12-week clinical trial of pemvidutide in MASLD was published in the Journal of Hepatology
The Phase 1 trial, which enrolled 94 subjects, evaluated three doses of pemvidutide versus placebo administered once weekly for 12 weeks.
Pemvidutide-treated subjects achieved up to 68.5% relative reduction in LFC, an important predictor of MASH resolution and fibrosis improvement, compared to 4.4% in subjects receiving placebo, with up to 55.6% of pemvidutide-treated subjects achieving LFC normalization.
LFC changes were accompanied by significant improvements in body weight and non-invasive markers of liver inflammation.
The adverse event discontinuation rate was only 2.9% in subjects receiving pemvidutide with no severe or serious adverse events reported.
The Company continues to advance IMPACT, its biopsy-driven Phase 2b trial of pemvidutide in MASH
The trial expects to enroll approximately 190 subjects with and without type 2 diabetes (T2D), randomized to receive 1.2mg or 1.8mg of pemvidutide or placebo.
The primary efficacy measures are MASH resolution or fibrosis improvement at Week 24.
The biopsy readout at Week 24 represents the earliest time point of any incretin-based MASH clinical trial.
Financial Results for the Three Months Ended June 30, 2024

Altimmune had cash, cash equivalents and short-term investments totaling $164.9 million on June 30, 2024.
Research and development expenses were $21.2 million for the three months ended June 30, 2024, compared to $13.3 million in the same period in 2023. The expenses for the quarter ended June 30, 2024, included $13.8 million in direct costs related to development activities for pemvidutide and $1.0 million in direct costs related to winddown and closing of our HepTcell program as announced on March 27, 2024.
General and administrative expenses were $5.6 million for the three months ended June 30, 2024, compared to $4.8 million in the same period in 2023. The increase was primarily due to a $1.0 million increase in stock compensation expense caused by modifications of stock awards.
Interest income for the three months ended June 30, 2024, was $2.2 million as compared to $1.8 million in the same period in 2023, primarily due to an increase in interest income earned on cash equivalents and short-term investments.
Net loss for the three months ended June 30, 2024, was $24.6 million, or $0.35 net loss per share, compared to a net loss of $16.1 million, or $0.32 net loss per share, in the same period in 2023.

On August 8, 2024 Akebia Therapeutics, Inc. (Nasdaq: AKBA), a biopharmaceutical company with the purpose to better the lives of people impacted by kidney disease, reported financial results for the second quarter ended June 30, 2024, and recent business highlights (Press release, Akebia, AUG 8, 2024, View Source [SID1234645582]). During the quarter, Akebia made significant progress across multiple initiatives related to the commercial launch of Vafseo (vadadustat) Tablets recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of anemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least three months.

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"Since receiving FDA approval in late March, our key priority has been to execute on our launch strategy developed with a goal for Vafseo to become the standard of care in the treatment of anemia for dialysis patients," said John P. Butler, Chief Executive Officer of Akebia. "Our team is actively engaged with prescribers, and I’m extremely encouraged by the positive reception we’ve seen across the kidney community for a new choice in anemia management. Equally important, our commercial team is now in active discussions with dialysis organizations covering the vast majority of patients to contract both Auryxia (ferric citrate) and Vafseo, giving our team a unique opportunity to contract across the portfolio."

Vafseo Global Launch Activities

•In June, Akebia submitted its Transitional Drug Add-on Payment Adjustment (TDAPA) application. Akebia expects to have Healthcare Common Procedure Coding System (HCPCS) codes assigned in October 2024 and TDAPA designation by January 1, 2025.
•Akebia set the Vafseo wholesale acquisition cost (WAC) at $1,278 for a 30-day supply at the labeled starting dose, or approximately $15,500 per year. All Vafseo sales in dialysis will be under contracts that include an off-invoice discount as well as volume-based tier discounts off the WAC price.
•Akebia partner MEDICE Arzneimittel Pütter GmbH&Co.KG (Medice) launched Vafseo in Germany and Austria in June and in the Netherlands in August.
•In July, Akebia regained full rights to sell Vafseo in the U.S. and is now able to contract directly with all dialysis organizations following the execution of a royalty-based termination agreement with CSL Vifor to simplify operational execution and improve economics.

Corporate Updates

In June, Erik Ostrowski joined Akebia as Senior Vice President, Chief Financial Officer and Chief Business Officer. Mr. Ostrowski brings over 20 years of finance and biotech operating experience, with a background in investment banking, including as a director of healthcare investment banking at Leerink Partners. He brings an impressive track record of corporate development leadership and strategic transaction execution.
Akebia reported second quarter 2024 Auryxia net product revenues of $41.2 million. Akebia expects Auryxia full year 2024 net product revenues to be in line with 2023 Auryxia net product revenue levels. Akebia’s commercial organization is heavily engaged in efforts to contract Auryxia through dialysis organizations in 2025, as phosphate binders are expected to be added to the Centers for Medicare & Medicaid Services bundled payment for dialysis care in January 2025.
Financial Results
•Revenues: Total revenues were $43.6 million in the second quarter of 2024 compared to $56.4 million in the second quarter of 2023. The decrease was driven by a reduction in license, collaboration and other revenue, which included a one-time $10 million upfront payment related to our Medice license agreement in the second quarter of 2023.

▪Net product revenues were $41.2 million in the second quarter of 2024 compared to $42.2 million in the second quarter of 2023.

▪License, collaboration and other revenues were $2.4 million in the second quarter of 2024 compared to $14.1 million in the second quarter of 2023.

•Cost of Goods Sold: Cost of goods sold (COGS) was $17.0 million in the second quarter of 2024 compared to $17.3 million in the second quarter of 2023. Akebia continues to carry a non-cash intangible amortization charge of $9.0 million per quarter in COGS through the fourth quarter of 2024.

•Research & Development Expenses: Research and development expenses were $7.6 million in the second quarter of 2024 compared to $20.2 million in the second quarter of 2023. The decrease was largely due to the completion of activities related to certain clinical trials, a reduction in consulting expenses and lower headcount related costs.

•Selling, General & Administrative Expenses: Selling, general and administrative expenses were $26.9 million for the second quarter of 2024 compared to $27.0 million in the second quarter of 2023.

•Net Loss: Net loss was $8.6 million in the second quarter of 2024 compared to $11.2 million in the second quarter of 2023.

•Cash Position: Cash and cash equivalents as of June 30, 2024 were $39.5 million. Akebia expects its existing cash resources and cash from operations will be sufficient to fund its current operating plan, including the U.S. Vafseo launch, for at least two years.
Conference Call
Akebia will host a conference call on Thursday, August 8 at 8:00 a.m. Eastern Time to discuss second quarter 2024 earnings. To access the call, please dial (800) 715-9871 (USA & Canada – Toll-Free) and enter Conference ID: 4155557.

On August 8, 2024 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, reported a financial and corporate update in conjunction with the Company’s 10-Q filing for the quarter ended June 30, 2024 (Press release, Foghorn Therapeutics, AUG 8, 2024, View Source [SID1234645598]). With an initial focus in oncology, Foghorn’s Gene Traffic Control Platform and resulting broad pipeline have the potential to transform the lives of people suffering from a wide spectrum of diseases.

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"We anticipate topline data from our Phase 1 combination trial with FHD-286 in patients with relapsed and/or refractory AML in the fourth quarter of 2024. We believe FHD-286 has the potential to be a first-in-class, mutation-agnostic differentiation therapeutic," said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. "Additionally, the IND for FHD-909 cleared in May and we anticipate FHD-909 to be the first SMARCA2 selective inhibitor to enter the clinic. Dosing of the first patient in our Phase 1 trial, with primary target population in SMARCA4 mutated NSCLC, is planned for the second half of the year. We are also on track to initiate IND-enabling studies in the fourth quarter of 2024 for our Selective CBP degrader program targeting tumors harboring EP300 mutations including bladder, gastric and endometrial cancers."

Mr. Gottschalk continued, "The biological foundation for the development of therapeutics targeting the chromatin regulatory system in oncology and other disease areas continues to get stronger. In April, we were pleased to present preclinical data at AACR (Free AACR Whitepaper) reinforcing the potential of our platform to deliver innovative medicines across cancers by selectively drugging historically very challenging targets. The conviction in our pipeline was further strengthened by our recent successful financing with new and long-term investors, which extended our expected cash runway into 2027 and through key inflection points, strongly positioning us for continued advancement."

Corporate Updates

Strengthened Balance Sheet to Advance Pipeline. In May, Foghorn successfully closed an approximately $110 million registered direct offering to advance the Company’s pipeline. The offering included new investors BVF Partners, Deerfield Management and other leading healthcare specialist investors as well as current investors, including founding investor Flagship Pioneering.

Presented at AACR (Free AACR Whitepaper) Annual Meeting. In April, Foghorn presented preclinical data highlighting pipeline progress on the advancement of multiple potential first-in-class medicines, including the first presentation of preclinical data for FHD-909, at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting.

Hosted Chromatin Regulation Summit. In April, Foghorn hosted the first Future of Disease and Chromatin Regulation Summit at the Foghorn corporate headquarters in Cambridge, Massachusetts. The live event featured presentations and panel discussions with world-renowned industry and academic key opinion leaders on therapeutic opportunities in chromatin regulatory biology.

Strengthened Executive Leadership. In April, Foghorn appointed Kristian Humer as Chief Financial Officer. Mr. Humer joined Foghorn with over 14 years of diversified financial strategy and business development experience in the life science industry and more than 20 years of experience in the financial industry.

Key Recent Program Updates and Upcoming Milestones

FHD-286. FHD-286 is a potent, first-in-class, selective inhibitor of the SMARCA2 (BRM) and SMARCA4 (BRG1) subunits of the BAF chromatin remodeling complex where dependency on SMARCA2/SMARCA4 is well-established preclinically with multiple tumor types, including acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS), non-small cell lung cancer (NSCLC) and prostate cancer.
•AML Phase 1 trial. The ongoing Phase 1 dose escalation trial is evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of FHD-286 in combination with decitabine or low-dose cytarabine in patients with relapsed and/or refractory AML who have failed multiple previous courses of therapy. FHD-286 previously demonstrated a promising mutation-agnostic differentiation effect in a single-agent dose escalation trial.
◦Topline clinical data are anticipated in the fourth quarter. We anticipate this will include topline safety, tolerability, initial efficacy and PK/PD data.

•Overcoming Tyrosine Kinase Inhibitor Resistance. Data published in Cancer Cell in August 2023, together with additional preclinical studies conducted by Foghorn, suggest that FHD-286 may play an important role in overcoming resistance in EGFR/KRAS tumors. Preclinical data profiling the ability of FHD-286 to amplify and/or restore tumor sensitivity will be presented with FHD-286 Phase 1 dose escalation data.

FHD-909. FHD-909 is a first-in-class oral SMARCA2 (BRM) selective inhibitor that has demonstrated in preclinical studies to have high selectivity over its closely related paralog SMARCA4 (BRG1), two proteins that are the catalytic engines across all forms of the BAF complex. SMARCA4 mutations are common across tumor types, including approximately 10% of NSCLC, and result in tumors being dependent on SMARCA2 activity for their survival. Selectively blocking SMARCA2 activity is a promising synthetic lethal strategy intended to induce tumor death while sparing healthy cells.
•In December 2021, Foghorn announced a strategic collaboration with Lilly to create novel oncology medicines. The collaboration includes a U.S. 50/50 co-development and co-commercialization agreement for Foghorn’s Selective SMARCA2 oncology program, which includes a selective inhibitor and a selective degrader, and an additional undisclosed oncology target. In addition, the collaboration includes three discovery programs using Foghorn’s proprietary Gene Traffic Control platform.
•In April 2024, Foghorn and Lilly presented new preclinical data as a poster presentation at the AACR (Free AACR Whitepaper) Annual Meeting and during a pipeline update call demonstrating at tolerable doses high SMARCA2 selectivity and dose-dependent single agent activity in SMARCA4 mutated cancers.
•In May 2024, the investigational new drug (IND) application was approved by the Food and Drug Administration. The primary target patient population is SMARCA4 mutated NSCLC.
•Dosing of the first patient in the Phase 1 trial for FHD-909 is planned to begin in the second half of 2024.

Selective CBP degrader program and Selective EP300 degrader program.
Foghorn is advancing two separate programs targeting either CBP or EP300, paralog histone acetyltransferases with a synthetic lethal relationship in tumor cells. Attempts to selectively drug CBP or EP300 have been challenging due to the high level of similarity between the two proteins. Additionally, dual inhibition of CBP/EP300 has been historically limited by hematopoietic toxicity.

Selective CBP degrader program. In April, Foghorn presented new pharmacodynamic and pharmacokinetic preclinical data at the 2024 AACR (Free AACR Whitepaper) Annual Meeting and during a pipeline update call highlighting:
•Deep and sustained CBP degradation significantly inhibited tumor growth in mouse xenograft solid tumor models.
•Robust monotherapy preclinical anti-tumor activity that was not associated with significant body weight loss, thrombocytopenia or anemia.
•Identification of potent and selective CBP protein degraders with first-in-class potential to address tumors harboring EP300 mutations in many types of cancer, including bladder, gastric and endometrial cancers.
•IND-enabling studies on track to initiate by the fourth quarter of 2024.

Selective EP300 degrader program. In April, Foghorn presented new pharmacodynamic and pharmacokinetic preclinical data at the 2024 AACR (Free AACR Whitepaper) Annual Meeting and during a pipeline update call highlighting:
•Well-tolerated in vivo with no observed decrease in platelet levels, with no effects on megakaryocyte viability at pharmacologically relevant concentrations in ex vivo studies.
•Identification of potent and selective EP300 degraders with anti-tumor activity in prostate and hematological malignancies, including prostate cancer, multiple myeloma and diffuse large B cell lymphoma (DLBCL).

Selective ARID1B degrader program.
ARID1A is the most mutated subunit in the BAF Complex and amongst the most mutated proteins in oncology. These mutations lead to a dependency on ARID1B, in several types of cancer, including ovarian, endometrial, colorectal and bladder. Attempts to selectively drug ARID1B have been challenging because of the high degree of similarity between ARID1A and ARID1B and the fact that ARID1B has no enzymatic activity to target.
•In April, Foghorn presented data at the AACR (Free AACR Whitepaper) Annual Meeting demonstrating potent and selective small molecule binders to ARID1B. The Company is in the process of converting these selective binders into heterobifunctional degraders.

Second Quarter 2024 Financial Highlights

•Collaboration Revenues. Collaboration revenue was $6.9 million for the three months ended June 30, 2024, compared to $5.6 million for the three months ended June 30, 2023. The increase year-over-year was primarily driven by the continued advancement of programs under the Lilly Collaboration Agreement.

•Research and Development Expenses. Research and development expenses were $23.8 million for the three months ended June 30, 2024, compared to $29.2 million for the three months ended June 30, 2023. This decrease was primarily due to lower personnel-related costs and lower development program spend following the shutdown of two clinical studies (FHD-286 in metastatic uveal melanoma and FHD-609 (BRD9 degrader) in synovial sarcoma).

•General and Administrative Expenses. General and administrative expenses were $7.3 million for the three months ended June 30, 2024, compared to $8.4 million for the three months ended June 30, 2023. This decrease was primarily due to lower personnel-related costs.

•Net Loss. Net loss was $23.0 million for the three months ended June 30, 2024, compared to a net loss of $29.5 million for the three months ended June 30, 2023.

•Cash, Cash Equivalents and Marketable Securities. As of June 30, 2024, the Company had $285.2 million in cash, cash equivalents and marketable securities, providing expected cash runway into 2027.

About FHD-286
FHD-286 is a highly potent, first-in-class, selective, allosteric, and orally available small-molecule, enzymatic inhibitor of SMARCA2 (BRM) and SMARCA4 (BRG1), two highly similar proteins that are the ATPases, or the catalytic engines, of the BAF complex, one of the key regulators within the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors.

About AML
Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.

About FHD-909
FHD-909 (LY4050784) is a potent, first-in-class, allosteric and orally available small molecule that selectively inhibits the ATPase activity of SMARCA2 (BRM) over its closely related paralog SMARCA4 (BRG1), two proteins that are the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, tumors with mutations in SMARCA4 rely on SMARCA2 for BAF function. FHD-909 has shown significant anti-tumor activity across multiple SMARCA4-mutant lung tumor models.

On August 8, 2024 Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, reported business highlights and financial results for the second quarter that ended June 30, 2024 (Press release, Monte Rosa Therapeutics, AUG 8, 2024, View Source [SID1234645615]).

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"The IND clearance of our VAV1-directed MGD MRT-6160 represents a major corporate milestone for Monte Rosa, signifying what we believe to be the first clinical-stage, rationally designed MGD for a non-oncology indication," said Markus Warmuth, M.D., Chief Executive Officer of Monte Rosa Therapeutics. "Our MRT-2359 program for MYC-driven solid tumors is in an ongoing Phase 1/2 study and we look forward to announcing the recommended Phase 2 dose, sharing updated clinical efficacy and safety results from the dose escalation arm of the trial, and initiating enrollment of our Phase 2 expansion cohorts in the second half of the year. Our second immunology/inflammation program, MRT-8102, a NEK7-directed MGD targeting diseases driven by IL-1β and the NLRP3 inflammasome, continues to advance and we expect to submit an IND application in the first half of next year. Our strategic collaboration with Roche has been progressing rapidly, and we are very pleased to announce today that we have reached our first set of research milestones, which we believe further validates the productivity of our QuEEN Discovery Engine. Our strong balance sheet, augmented by our recent financing, is expected to provide cash runway into H1 2027, funding the Company through multiple anticipated milestones including proof-of-concept readouts for our three lead programs."

RECENT HIGHLIGHTS

MRT-2359, GSPT1-directed MGD for MYC-driven solid tumors

•
Monte Rosa continues to evaluate MRT-2359 in a Phase 1/2 clinical trial in MYC-driven solid tumors (NCT05546268). In June 2024, the Company announced that it had obtained encouraging initial safety and pharmacodynamic data from the 0.5 mg dose using the 21 days on, 7 days off regimen. This regimen represents dosing of MRT-2359 twice as frequently per cycle compared to the 5 days on, 9 days off regimen previously evaluated in this study. Based on the favorable safety assessment for the 0.5 mg dose, the Company continues to evaluate a higher 0.75 mg, 21 days on, 7 days off dose cohort. In the second half of the year, Monte Rosa expects to make a final determination of the MRT-2359 recommended Phase 2 dose, share updated clinical activity and safety results from the dose escalation arm of the trial, and initiate enrollment of MRT-2359 Phase 2 expansion cohorts.
MRT-6160, VAV1-directed MGD for systemic and neurological autoimmune/inflammatory diseases

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Monte Rosa reported that its Investigational New Drug (IND) submission for MRT-6160 has been accepted by the U.S. Food and Drug Administration (FDA). Initiation of a Phase 1 single ascending dose/multiple ascending dose (SAD/MAD) study is expected this summer and initial clinical results are anticipated in Q1 2025.
•
In July, Monte Rosa reported the publication of a review article titled, VAV1 as a putative therapeutic target in autoimmune and chronic inflammatory diseases, co-authored by Prof. Dr. Markus F. Neurath, Friedrich-Alexander-University Erlangen-Nürnberg, and Prof. Leslie J. Berg, University of Colorado School of Medicine, in the peer-reviewed journal Trends in Immunology, a Cell Press journal. The publication highlights how novel approaches targeting VAV1 have therapeutic potential in T and B-cell-mediated autoimmune and chronic inflammatory diseases.
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In June, Monte Rosa presented preclinical data at the EULAR 2024 conference demonstrating that MRT-6160 inhibited disease progression, pro-inflammatory cytokines, and autoantibody production in the collagen-induced arthritis murine model of rheumatoid arthritis.
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In May, Monte Rosa presented preclinical data at Digestive Disease Week 2024 demonstrating that MRT-6160 inhibited colitis disease progression and colon inflammation, lowered inflammatory mucosal cytokines, and reduced expression of IBD-associated genes in a T-cell transfer murine model of colitis.
MRT-8102, NEK7-directed MGD for inflammatory diseases driven by IL-1β and the NLRP3 inflammasome

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In March, Monte Rosa announced the initiation of IND-enabling studies for MRT-8102, a first-in-class NEK7-directed MGD for the treatment of inflammatory diseases driven by interleukin-1β (IL-1β) and the NLRP3 inflammasome, critical elements of the inflammatory process. MRT-8102 has demonstrated highly favorable central nervous system (CNS) exposure and degradation in a study in non-human primates, supporting its potential development in neurologic indications and obesity, in addition to potential use in gout, pericarditis, and other peripheral inflammatory conditions. The Company is evaluating applications across multiple inflammatory disorders.
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Monte Rosa expects to submit an IND application for MRT-8102 in H1 2025.
CDK2 and Cyclin E1-directed MGD programs

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In May, Monte Rosa announced a new discovery program for CCNE1 (Cyclin E1)-directed MGDs for the treatment of CCNE1-amplified tumors. CCNE1, a key component of the cell cycle and a known driver of many cancers, is generally considered an undruggable target by conventional modalities.
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Monte Rosa is progressing both programs to development candidate nominations and expects to nominate a development candidate for the CDK2-directed MGD program by year end.
Additional Corporate Updates

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Monte Rosa announced today that it achieved pre-specified research milestones and earned milestone payments under its strategic collaboration and licensing agreement with Roche. In October 2023, Monte Rosa entered into a strategic collaboration and licensing agreement with Roche to discover and develop MGDs against targets in cancer and neurological diseases. Under the terms of the agreement, Monte Rosa received an upfront payment of $50 million and is eligible to receive future preclinical, clinical, commercial, and sales milestone payments that could exceed $2 billion, as well as tiered royalties.

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In May, the Company announced an underwritten public offering providing gross proceeds of approximately $100 million.
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In May, Monte Rosa announced three leadership team promotions: Sharon Townson, Ph.D., to Chief Scientific Officer; Phil Nickson, Ph.D., J.D., to Chief Business and Legal Officer; and Jennifer Champoux to Chief Operating Officer.
ANTICIPATED MILESTONES

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Announce the recommended Phase 2 dose for the MRT-2359 Phase 1/2 study and report Phase 1 clinical activity and safety results in H2 2024. The Company also plans to initiate the Phase 2 portion of the study before year-end. The Company is evaluating Phase 2 expansion cohorts in high-prevalence c-MYC-driven tumors, including hormone receptor-positive breast cancer and prostate cancer, as well as tumor types and patient populations driven by L- and N-MYC including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and solid tumors with amplifications of L- and N-MYC.
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Initiate a Phase 1 SAD/MAD study with MRT-6160 in healthy volunteers in mid-2024; report results from the Phase 1 study in Q1 2025. Monte Rosa expects to subsequently initiate proof-of-concept (POC) studies in autoimmune/inflammatory diseases, including ulcerative colitis and rheumatoid arthritis, with additional potential POC studies in dermatology, rheumatology, and neurology indications.
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Submit an IND application for MRT-8102 in H1 2025.
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Nominate a development candidate for the CDK2 preclinical program in 2024.

SECOND QUARTER 2024 FINANCIAL RESULTS

Collaboration Revenue: Collaboration revenue for the second quarter of 2024 was $4.7 million, compared with $0 during the same period in 2023. Collaboration revenue represents revenue recorded under the Roche License and Collaboration agreement.

Research and Development (R&D) Expenses: R&D expenses for the second quarter of 2024 were $28.1 million, compared to $29.1 million during the same period in 2023. R&D expenses were driven by the successful achievement of key milestones in our R&D organization, including the continuation of the MRT-2359 clinical study, the progression and growth of our preclinical pipeline, the preparation of MRT-6160 to enter the clinic, and the continued development of the Company’s QuEEN discovery engine. Non-cash stock-based compensation constituted $2.6 million of R&D expenses for Q2 2024, compared to $2.3 million in the same period in 2023.

General and Administrative (G&A) Expenses: G&A expenses for the second quarter of 2024 were $9.3 million compared to $8.1 million during the same period in 2023. The increase in G&A expenses resulted from increased headcount, stock-based compensation expense, and fees paid to consultants to support growth and operations. G&A expenses included non-cash stock-based compensation of $1.9 million for the second quarter of 2024, compared to $1.9 million for the same period in 2023.

Net Loss: Net loss for the second quarter of 2024 was $30.3 million, compared to $32.0 million for the first quarter of 2024.

Cash Position and Financial Guidance: Cash, cash equivalents, restricted cash, and marketable securities as of June 30, 2024, were $267.1 million, compared to cash, cash equivalents, restricted cash, and marketable securities of $197.8 million as of March 31, 2024.

The Company expects its cash and cash equivalents to be sufficient to fund planned operations and capital expenditures into the first half of 2027.

About MRT-2359

MRT-2359 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that induces the interaction between the E3 ubiquitin ligase component cereblon and the translation termination factor GSPT1, leading to the targeted degradation of GSPT1 protein. The MYC transcription factors (c‑MYC, L-MYC and N-MYC) are well-established drivers of human cancers that maintain high levels of protein translation, which is critical for uncontrolled cell proliferation and tumor growth. Preclinical studies have shown this addiction to MYC-induced protein translation creates a dependency on GSPT1. By inducing degradation of GSPT1, MRT-2359 is designed to exploit this vulnerability, disrupting the protein synthesis machinery, leading to anti-tumor activity in MYC-driven tumors.

About MRT-6160

MRT-6160 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader of VAV1, which in preclinical studies has shown deep degradation of its target with no detectable effects on other proteins. VAV1, a Rho-family guanine nucleotide exchange factor, is a key signaling protein downstream of both the T- and B-cell receptors. VAV1 expression is restricted to blood and immune cells, including T and B cells. Preclinical studies have shown that targeted degradation of VAV1 protein via an MGD modulates both T- and B-cell receptor-mediated activity. This modulation is evident both in vitro and in vivo, demonstrated by a significant decrease in cytokine secretion, proteins vital for maintaining autoimmune diseases. Moreover, VAV1-directed MGDs have shown promising activity in preclinical models of autoimmune diseases and thus have the potential to provide therapeutic benefits in multiple systemic and neurological autoimmune indications, such as inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and dermatological disorders. Preclinical studies have demonstrated that MRT-6160 can inhibit disease progression in several in vivo autoimmunity models.

About MRT-8102

MRT-8102 is a potent, highly selective, and orally bioavailable investigational molecular glue degrader (MGD) that targets NEK7 for the treatment of inflammatory diseases driven by IL-1β and the NLRP3 inflammasome. NEK7 has been shown to be required for NLRP3 inflammasome assembly, activation and IL-1β release both in vitro and in vivo. Aberrant NLRP3 inflammasome activation and the subsequent release of active IL-1β and interleukin-18 (IL-18) has been implicated in multiple inflammatory disorders, including gout, cardiovascular disease, neurologic disorders including Parkinson’s disease and Alzheimer’s disease, ocular disease, diabetes, obesity, and liver disease. In a non-human primate model, MRT-8102 was shown to potently, selectively, and durably degrade NEK7, and resulted in near-complete reductions of IL-1β models following ex vivo stimulation of whole blood. MRT-8102 has shown a favorable profile in non-GLP toxicology studies.

On August 8, 2024 Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported that it has entered into a strategic financing agreement with Sixth Street for significant, long-term, non-dilutive capital to fund innovation and growth opportunities across Arrowhead’s robust and diverse pipeline of RNAi therapeutics (Press release, Arrowhead Pharmaceuticals, AUG 8, 2024, View Source [SID1234645642]). The $500 million senior secured credit facility includes $400 million funded at close with an additional $100 million available at Arrowhead’s option, subject to mutual agreement between Sixth Street and Arrowhead, during the seven-year term of the agreement.

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"This deal and its favorable structure and economics allow us to confidently build our commercial capabilities to support our first commercial launch in 2025, provided we receive regulatory approval for plozasiran in familial chylomicronemia syndrome. This transaction is non-dilutive and has an attractive repayment structure, which largely aligns outflows with future inflows, allowing us to keep more cash in the business at a critical time of growth. In addition, because of the flexible repayment mechanics during the seven-year term, it has important risk sharing features. Not only does the facility allow us to support plozasiran as we move toward a commercial launch, it also expands our ability to fund growth and innovation across our pipeline," said Christopher Anzalone, Ph.D., President and CEO at Arrowhead.

Jeff Pootoolal, Partner at Sixth Street and Michael Reslinski, Managing Director added, "Arrowhead Pharmaceuticals has an impressive platform technology, attractive pipeline assets with promising commercial opportunities, and multiple partnerships maturing toward commercialization. We are pleased to utilize our firm’s scale, expertise and flexibility to help Arrowhead meet its strategic objectives through this innovative financing solution, and we hope to continue strengthening our relationship with the company as it rapidly becomes one of the most exciting emerging commercial-stage biopharmaceutical companies."

The credit facility matures on August 7, 2031, and bears interest at an annual rate of 15%. The credit facility does not provide for scheduled amortization payments during the term, and all principal will be due on the Maturity Date. Arrowhead will have the right to prepay loans under the credit facility at any time. The company is required to partially repay loans under the credit facility with a portion of the proceeds from certain transactions, such as the future collection of upfront payments, milestones, and royalties from partnerships and collaborations, and commercial revenue by Arrowhead. All obligations will be secured on a first-priority basis, subject to certain exceptions, by security interests in substantially all assets of the company.

TD Cowen acted as financial advisor and Gibson, Dunn & Crutcher LLP served as legal advisor to Arrowhead. Proskauer Rose LLP and Mintz, Levin, Cohn, Ferris, Glovsky & Popeo, PC acted as legal advisors to Sixth Street.