On May 9, 2024 OmniAb, Inc. (NASDAQ: OABI) reported financial results for the three months ended March 31, 2024, and provided operating and partner program updates (Press release, OmniAb, MAY 9, 2024, View Source [SID1234643045]).

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"The OmniAb team continued to make great progress this past quarter in advancing and expanding our portfolio and partnership base. We added three new platform license agreements in the first quarter, bringing our total active partners to 80, net of attrition," said Matt Foehr, Chief Executive Officer of OmniAb. "We have built our company upon a differentiated suite of technologies and a highly scalable and leverageable business model, and our growth during the past 18 months reflects the strength of our offering to the industry. We’re off to a strong start in 2024 and we look forward to continued progress by our partners and expansion of our technology as the year progresses."

First Quarter 2024 Financial Results

Revenue for the first quarter of 2024 was $3.8 million, compared with $16.9 million for the same period in 2023, with the decrease primarily due to the recognition in the 2023 period of a $10 million milestone related to the first commercial sale of TECVAYLI (teclistamab) in the EU and lower service revenue in the 2024 period as a result of the completion of discovery work on certain ion channel programs.

Research and development expense was $14.6 million for the first quarter of 2024, compared with $13.8 million for the same period in 2023, with the increase primarily due to higher personnel costs. General and administrative expense was $8.3 million for the first quarter of 2024, compared with $8.2 million for the same period in 2023.

Net loss for the first quarter of 2024 was $19.0 million, or $0.19 per share, compared with a net loss of $6.1 million, or $0.06 per share, for the same period in 2023.

As of March 31, 2024, OmniAb had cash, cash equivalents and short-term investments of $69.0 million.

2024 Financial Guidance

OmniAb continues to expect operating expense in 2024 to be approximately the same as in 2023, as the Company is now staffed and resourced to leverage the future growth of the business.

OmniAb continues to expect its cash use in 2024 to be relatively similar to its cash use in 2023, excluding the $35 million TECVAYLI milestone payment received in 2023. Given the expected progression of the existing partnered pipeline, OmniAb expects its cash use in 2025 to be substantially lower than in 2024. OmniAb’s current cash balance and cash from operations are expected to provide sufficient capital to fund operations for the foreseeable future.

First Quarter 2024 and Recent Business Highlights

During the first quarter of 2024, OmniAb signed three new license agreements including ImmunoBiochem Corporation, the University of Georgia and a stealth Boston-based venture-backed start-up. As of March 31, 2024, the Company had 80 active partners and 327 active programs, including 31 OmniAb-derived programs in clinical development or being commercialized.

First quarter 2024 and recent partner highlights include the following:

Batoclimab

Immunovant reported that global Phase 3 clinical trials of batoclimab (anti-FcRn) in myasthenia gravis (MG) and thyroid eye disease (TED) are progressing and are on track for topline data readout in the second half of 2024 (MG) and the first half of 2025 (TED). Initial period 1 data from the Phase 2b clinical trial in chronic inflammatory demyelinating polyneuropathy are expected in the second or third quarter of 2024.
HanAll Biopharma announced that in collaboration with Immunovant, the Phase 3 clinical study is progressing in generalized myasthenia gravis in Japan. HanAll also reported that a clinical trial notification was approved to initiate a Phase 3 clinical study of batoclimab in TED in Japan.
IMVT-1402

Immunovant announced plans to initiate four to five potential registrational programs for IMVT-1402 (second-generation anti-FcRn) during its fiscal year ending March 31, 2025. The company also plans on initiating trials in 10 indications for IMVT-1402 over its next two fiscal years.
Immunovant announced that the United States Patent and Trademark Office has issued U.S. Patent No. 11,926,669 ("the ‘669 patent") for IMVT-1402. The allowed claims cover composition of matter for the binding sequence of IMVT-1402 to FcRn, method of use of the antibody for treating autoimmune disease, as well as methods for its manufacturing. Not including any potential patent term extension, the ‘669 patent will expire on June 23, 2043.
M9140

At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, Merck KGaA presented data on M9140, a novel antibody-drug conjugate with topoisomerase 1 inhibitor payload targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expressing tumors.​ M9140 demonstrated high potency, strong antitumor activity and bystander effect in preclinical models.
A first-in-human Phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary clinical activity of M9140 in patients with advanced solid tumors is ongoing.
Acasunlimab

Genmab expects to announce acasunlimab (GEN1046: PD-L1 x 4-1BB) Phase 2 data in second-line non-small cell lung cancer (NSCLC) in the first half of 2024.
A poster titled "Acasunlimab (duobody-PD-L1x4-1BB) alone or in combination with pembrolizumab in patients with previously treated metastatic non-small cell lung cancer: Initial results of a randomized, open-label, Phase 2 trial" will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024 at 9:00 a.m. Central time on Saturday, June 1, 2024.
In addition, Genmab plans to initiate a Phase 3 study of acasunlimab in second-line NSCLC in 2024.
Sugemalimab

CStone announced the National Medical Products Administration of China has approved the supplemental biologics application for sugemalimab (Cejemly) in combination with fluorouracil and platinum-based chemotherapy as first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma with a PD-L1 expression (Combined Positive Score [CPS] ≥5). Sugemalimab is the first PD-L1 monoclonal antibody approved for this indication.
CStone also announced that the results of the progression-free survival final analysis and the overall survival interim analysis in the registrational GEMSTONE-304 study for unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma were published in Nature Medicine.
OmniAb scientists published a peer-reviewed paper in the Journal of Immunology demonstrating that chickens can be genetically engineered to produce functional single-domain antibodies (sdAbs). This modality, produced naturally by camelids, has gained popularity as a small, robust and highly versatile building block for antibody discovery, especially in constructing multi-specifics and CAR-T cells. These data supported the feasibility of the Company’s next-generation transgenic chicken OmnidAb that produces fully human stabilized sdAbs. The OmnidAb platform was launched during the fourth quarter of 2023.

OmniAb will highlight some of its high-throughput single cell screening xPloration data at the 20th Annual PEGS Boston Conference and Expo, where Bob Chen, Ph.D., Senior Director, Discovery Systems, will give a presentation titled "Deep Screening in Harmony with Artificial Intelligence for Bispecific Antibody Discovery" at 12:20 p.m. Eastern time on Wednesday, May 15, 2024.

The Company also expects that multiple partners will be presenting data from programs developed with OmniAb technology at the ASCO (Free ASCO Whitepaper) Annual Meeting taking place May 31 – June 4, 2024.

Conference Call and Webcast

OmniAb management will host a conference call with accompanying slides today beginning at 4:30 p.m. Eastern time (1:30 p.m. Pacific time) to discuss this announcement and answer questions. To participate via telephone, please dial (800) 549-8228 using the conference ID 08922. Slides, as well as the live and replay webcast of the call, are available at View Source

On May 9, 2024 Infinitopes Precision Immunomics, an integrated cancer biotech combining world leading platforms in precision antigen discovery with vaccine vectors capable of durably stimulating protective immune responses, reported the publication of a peer-reviewed article in Human Vaccines & Immunotherapeutics (HVI) (Press release, Infinitopes, MAY 9, 2024, View Source [SID1234643044]). The article outlines the current cancer vaccine landscape and the challenges facing vaccine technologies for the treatment of solid tumours to explain the advantages of Infinitopes’ combined approach to cancer vaccines: incorporating the right targets and the right vectors, for the right patients at the right time.

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The review, entitled "Unlocking Cancer Vaccine Potential: What are the Key Factors?", was an invited contribution from the editorial team at HVI for inclusion in their special edition on cancer vaccines. The Company co-authored the review in close collaboration with senior academics from the University of Oxford’s cancer vaccine programme. The article describes the history of cancer vaccine development, the impact of the SARS-CoV-2 pandemic on vaccine immunology, and the hurdles that face the successful clinical development of vaccines within the solid tumour space.

Limited understanding of tumour biology has historically been a major obstacle to progress in cancer vaccine development. Following the announcement of its £12.8m seed funding round in April 2024, Infinitopes is investing in world-leading mass spectrometry equipment to accurately identify the best synergistic tumour targets. This will enable the company to expand the development of its precision-targeted cancer vaccines for five further cancers beyond its lead candidate, which is due to begin phase I/IIa later this year.

Dr Jonathan Kwok, Infinitopes CEO, commented: "Infinitopes’ team has amassed an enormous wealth of insight into the fundamental immunology required to develop effective cancer vaccines. Over the past decade, we have crystallised our understanding of the building blocks necessary to design precision-targeted, durably stimulating, affordable vaccine therapies. It’s an honour to be invited to share our learnings with readers of the prestigious Human Vaccines & Immunotherapeutics journal, and we look forward to the future collaborations this will unlock."

Lead author Dr Michael Grant, Executive Medical Director of Infinitopes, commented: "The global burden of cancer is increasing, whilst advances in diagnosis and shifts in lifestyle factors are changing the demographics of patients that we see in clinic. There is a growing need for cost-effective treatments that can be deployed in the earlier stages of disease. Cancer vaccines offer a potential solution to this and, in the past few years alone, we have begun to see some exciting results from different vaccine platforms. However, it is vital that we learn from previous failures – as well as recent successes – to optimise the clinical development of future cancer vaccines."

Professor Mark Middleton, Head of the Department of Oncology at the University of Oxford and Scientific Advisory Board member for Infinitopes, added: "As we detect cancers earlier, we need treatments that are cheaper and better tolerated than existing drugs, and cancer vaccines look very promising. Recent trial results show that they work, and they are relatively cheap to make at scale. The challenge now is to understand the rules that govern vaccine activity, so we can give them to the right patients at the right time."

"Unlocking Cancer Vaccine Potential: What are the Key Factors?" is available to read online at:

View Source

On May 9, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer and rare diseases, reported new preclinical data supporting the potential of its fully non-viral lead genetic medicines programs and related platform technologies (Press release, Poseida Therapeutics, MAY 9, 2024, View Source [SID1234643043]). The data was included in three oral and three poster presentations at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2024 Annual Meeting, being held in Baltimore, MD and virtually on May 7-11, 2024.

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"Poseida’s unique and proprietary toolkit, which enables non-viral gene insertion, high-fidelity gene editing, and associated delivery and manufacturing technologies, has been the driving force behind our emerging genetic medicines programs and our clinical stage allogeneic CAR-T pipeline," said Blair Madison, Ph.D., Chief Scientific Officer, Gene Therapy at Poseida Therapeutics. "Starting with our recent R&D Day, and continuing with ASGCT (Free ASGCT Whitepaper), we have showcased the maturity and power of our tools specific to enabling a fully non-viral and potentially tunable approach to in vivo genetic medicine. We believe this could provide our medicines with a superior profile featuring a minimized risk of off-target effects that can be customized to each patient, when appropriate. Taken together, these data give us confidence as we continue to validate our non-viral approach, seeking to achieve durable correction in patients suffering from rare diseases such as Hereditary Angioedema and Hemophilia A."

Oral Presentations

Title: Highly Specific Non-Viral Gene Editing with P-KLKB1-101 for Hereditary Angioedema
Presenting Author: Blair Madison, Ph.D., Poseida Therapeutics, Inc.
Session Title: Correction of Genetic Disorders of the Blood and Immune System
Presentation Date/Time: Thursday, May 9, 2024, 1:30 – 1:45 PM ET
Location: Room 314-317
Abstract Number: 170

Hereditary Angioedema (HAE) is a rare inherited disorder characterized by recurrent episodes of fluid accumulation outside of blood vessels, causing rapid swelling of tissues. HAE patients have significant unmet need for a durable, effective, and convenient treatment option that eliminates recurrent attacks. P-KLKB1-101 is a fully non-viral investigational gene editing therapy designed to enable high fidelity editing at pre-kallikrein, or KLKB1, for targeted correction of HAE. It utilizes the Cas-CLOVER nuclease to achieve clean site-specific gene editing that is engineered for high specificity. In pre-clinical studies, P-KLKB1-101 demonstrates excellent efficiency editing liver cells with off-target edits <0.1% over a wide range of lipid nanoparticle (LNP) concentrations. Poseida’s gene editing delivery technologies, including novel ionizable lipid and LNP, enable a highly controlled dose response. Interim non-human primate (NHP) data demonstrate favorable tolerability and liver editing approaching the desired therapeutic range. Development of P-KLKB1-101 is ongoing, including continuation of dose-finding studies in NHPs, CMC manufacturing, scale-up, and additional preparations for IND-enabling studies.

Title: Sustained FVIII Expression with a Tolerable, Titratable, Fully Non-Viral Gene Therapy for Hemophilia A
Presenting Author: Brian Truong, Ph.D., Poseida Therapeutics, Inc.
Session Title: Liver Genetic Diseases
Presentation Date/Time: Thursday, May 9, 2024, 5:00 – 5:15 PM ET
Location: Room 324-326
Abstract Number: 210

P-FVIII-101 is a fully non-viral gene insertion-based therapy for the treatment of Hemophilia A, an X-linked bleeding disorder caused by a deficiency in coagulation Factor VIII (FVIII). It utilizes Poseida’s proprietary transposon technology combined with nanoparticle delivery to achieve site-specific gene insertion into DNA. Data demonstrate that a single dose of P-FVIII-101 achieves Hemophilia A disease correction with sustained FVIII expression observed over the 13-month duration of the mouse study. The pre-clinical data also support the potential for repeat dosing, enabled by the fully non-viral approach. P-FVIII-101 can also be combined with Poseida’s new proprietary modulator switch, which allows inducible down-regulation to enable patient-specific fine tuning of FVIII levels, which is seen as an important product attribute by the hemophilia community.

Development of P-FVIII-101 is ongoing with final optimization of the nanoparticle delivery modality to be validated in NHPs.

Title: A Durable Gene Therapy with a Robust AAV-LNP Delivery System Allowing for a Reduced AAV Dose
Presenting Author: Jack Rychak, Ph.D., Poseida Therapeutics, Inc.
Session Title: AAV Vectors – Preclinical and Proof-of-Concept: Technology Focus
Presentation Date/Time: Friday, May 10, 2024, 1:45 – 2:00 PM ET
Location: Ballroom 2
Abstract Number: 248

This presentation highlights data from studies exploring the feasibility of combining existing adeno-associated virus delivery vectors (AAVs) with Poseida’s piggyBac DNA insertion system. This approach is intended to achieve stable integration of a transgene into a large percentage of hepatocytes for maximal therapeutic benefit, which cannot be readily achieved using an AAV or episomal approach. Pre-clinical data demonstrate exceptional efficacy in mouse models of severe Ornithine Transcarbamylase Deficiency (OTCD). Additionally, robust potency is observed in mouse models of Phenylketonuria (PKU), using low AAV doses, and enabled by the integration of a therapeutic transgene with the SPB transposase. These data highlight the utility of the hybrid platform for enabling effective treatment with lower AAV doses, even in the growing liver early in life. With Poseida’s current internal focus on fully non-viral approaches, as announced at the Company’s recent R&D Day, the Company may opportunistically consider partnering transactions with respect to its P-PAH-101 and P-OTC-101 programs.

Poster Presentations

Title: Advanced Gene Editing with an Enhanced Site-Specific Nuclease for Knock-Out and Knock-In Applications
Presenting Author: Oscar Alvarez, Ph.D., Poseida Therapeutics, Inc.
Session Title: Wednesday Posters: Gene Targeting and Gene Correction New Technologies
Session Date/Time: Wednesday, May 8, 2024, 12:00 PM ET
Location: Exhibit Hall
Abstract Number: 717

Poseida’s Cas-CLOVER nuclease system represents a key advancement in gene editing technology with high-fidelity performance that significantly exceeds that of traditional nucleases. Poseida developed its Cas-CLOVER system by incorporating an S44P mutation which confers a two to three-fold improvement in on-target Cas-CLOVER editing efficiency, while fully preserving fidelity and with no increase in off-target editing. The enhanced Cas-CLOVER system exhibits remarkable capabilities for site-specific insertion of genes, as evidenced by the successful integration of a therapeutic transgene in mouse liver cells and associated phenotypical disease rescue in a PKU mouse model.

The Company plans to evaluate homology-independent targeting using its rapidly advancing fully non-viral DNA delivery technology for the precise insertion of genes and related gene expression regulators to specific sites in the genome.

Title: Optimizing Lipid Nanoparticle Formulations for Enhanced Non-Viral Gene Therapy: Overcoming DNA Delivery Challenges and Achieving High-Efficiency Transgene Integration
Presenting Author: George Wang, Ph.D., Poseida Therapeutics, Inc.
Session Title: Thursday Posters: Other Nonviral Delivery
Session Date/Time: Thursday, May 9, 2024, 12:00 PM ET
Location: Exhibit Hall
Abstract Number: 1239

This study demonstrates the optimization of DNA delivery to hepatocytes, in vivo, and genomic integration using Poseida’s piggyBac DNA insertion system. Poseida has synthesized and evaluated novel terpene-based lipids exhibiting unique DNA encapsulation and delivery properties in vivo. Poseida also identified a class of amphipathic small molecules called Poseida Delivery Excipients (PDEs) with unique capabilities for enhancing DNA delivery. Data demonstrated that inclusion of these PDEs in LNPs improved the insertion of targeted genes and decreased pro-inflammatory cytokine release. LNPs comprising novel ionizable lipids and PDEs also significantly enhanced genomic insertion of therapeutically relevant transgenes in vivo. These unique combinations of LNPs and PDEs could further enhance the potential of Poseida’s non-viral DNA platform technology and piggyBac DNA insertion system for treating serious genetic disorders.

Title: Novel Biodegradable Lipid Nanoparticles (LNP) for Co-Encapsulation of Complex Nucleic Acid Payloads for In Vivo Genome Editing
Presenting Author: Alicia Davis, Ph.D., Poseida Therapeutics
Session Title: Friday Posters: Other Nonviral Delivery
Session Date/Time: Friday, May 10, 2024, 12:00 PM ET
Location: Exhibit Hall
Abstract Number: 1737

This presentation highlights the development of an LNP capable of robustly co-encapsulating and delivering Poseida’s Cas-CLOVER nuclease system to the liver, while avoiding unintended uptake. Poseida has identified and characterized a novel class of biodegradable ionizable lipids for in vivo mRNA delivery. The Company has identified lipid S, which demonstrated potent mRNA delivery potency and improved clearance from the liver. These studies demonstrate Poseida’s discovery chemistry and formulation capabilities to generate high-performing LNPs for the efficient delivery of next-generation genetic medicine platforms such as Cas-CLOVER.

About P-KLKB1-101

P-KLKB1-101 is an investigational liver-directed non-viral gene editing approach designed using Cas-CLOVER Site-Specific Gene Editing System, Poseida’s proprietary high-fidelity nuclease, for site-specific gene editing of the KLKB1 gene, for the treatment of Hereditary Angioedema (HAE). HAE is a rare, inherited disorder that results in the swelling of the skin, intestinal tract, and airways, which can be both debilitating and life-threatening. Preclinical data demonstrate therapeutically relevant reduction of pre-kallikrein levels in both mouse and NHP models.

About P-FVIII-101

P-FVIII-101 is an investigational liver-directed gene insertion program combining Poseida’s non-viral transposon platform and nanoparticle delivery technologies for the in vivo treatment of Hemophilia A. Hemophilia A is a hereditary bleeding disorder caused by a deficiency in Factor VIII production with a high unmet need, resulting in excessive bleeding occurring either spontaneously or due to trauma and leading to pain and permanent joint damage in patients. P-FVIII-101 utilizes the piggyBac gene integration system delivered via lipid nanoparticle, which has demonstrated the potential to correct Factor VIII deficiency in juvenile and adult animal models using Poseida’s fully non-viral insertion system that is capable of whole gene correction.

On May 9, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported business updates and reported financial results for the first quarter ended March 31, 2024 (Press release, Verastem, MAY 9, 2024, View Source [SID1234643042]).

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"In the first quarter of 2024, we received FDA Orphan Drug Designation for avutometinib and defactinib combination in recurrent low-grade serous ovarian cancer, which recognizes this rare cancer as different and distinct from other forms of ovarian cancer and reinforces the need for new treatment options," said Dan Paterson, president and chief executive officer of Verastem Oncology. "We look forward to starting our planned rolling NDA submission and sharing topline data for avutometinib and defactinib combination in recurrent low-grade serous ovarian cancer. We also plan to announce initial data from the RAMP 205 trial in first-line metastatic pancreatic cancer at ASCO (Free ASCO Whitepaper) and plan to provide updates across our other clinical programs in the second half of 2024."

First Quarter 2024 and Recent Updates

Avutometinib and Defactinib Combination in Low-Grade Serous Ovarian Cancer (LGSOC)

Enrollment and site activations are underway in the U.S., Australia, and the UK, for the international confirmatory Phase 3 RAMP 301 trial evaluating the avutometinib and defactinib combination versus standard of care chemotherapy or hormonal therapy for the treatment of recurrent LGSOC.
Granted Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for avutometinib alone or in combination with defactinib for the treatment of all patients with recurrent LGSOC, in March 2024.
Multiple abstracts were selected for oral and poster presentations at the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer on March 16-18 in San Diego. These presentations included a late-breaking oral presentation on a planned subgroup analysis of Part A of the Phase 2 RAMP 201 trial of avutometinib and defactinib combination of heavily pretreated patients with LGSOC and a plenary oral presentation of preclinical efficacy data of avutometinib in combination with a focal adhesion kinase (FAK) inhibitor in recurrent LGSOC as well as a trials-in-progress poster about the Phase 3 RAMP 301 trial.
Plan to announce updated topline data from the RAMP 201 trial in LGSOC to coincide with the start of our planned rolling New Drug Application (NDA) submission for Accelerated Approval for the avutometinib and defactinib combination in recurrent LGSOC in Q2 2024.
Preparations for a potential U.S. commercial launch in 2025 are ongoing and plans to initiate discussions with European and Japanese regulatory authorities to address patient needs outside the U.S. continue to advance.
Avutometinib in Combination with KRAS G12C Inhibitors in Non-Small Cell Lung Cancer (NSCLC)

Verastem Oncology announced today it has received Fast Track Designation from the FDA for avutometinib in combination with Mirati’s (BMS) G12C inhibitor, KRAZATI (adagrasib) for the treatment of patients with KRAS G12C-mutated metastatic NSCLC who have received at least one prior systemic therapy and have not been previously treated with a KRAS G12C inhibitor, in April 2024.
Verastem Oncology announced today it has received Fast Track Designation from the FDA for the combination of avutometinib plus defactinib with Amgen’s G12C inhibitor, LUMAKRAS (sotorasib) for the treatment of patients with KRAS G12C-mutated metastatic NSCLC who have received at least one prior systemic therapy, in April 2024.
The FDA granted Fast Track Designation for avutometinib in combination with Amgen’s G12C inhibitor, LUMAKRAS (sotorasib), for the treatment of patients with KRAS G12C-mutant metastatic NSCLC who have received at least one prior systemic therapy and have not been previously treated with a KRAS G12C inhibitor, in January 2024.
Data updates from patients with KRAS G12C-mutant NSCLC in the Phase 1/2 RAMP 203 trial evaluating avutometinib plus defactinib and sotorasib are planned for H2 2024.
Data from patients with KRAS G12C-mutant NSCLC in the Phase 1/2 RAMP 204 trial evaluating avutometinib and adagrasib are planned for H2 2024.
Avutometinib and Defactinib Combination in First-Line Metastatic Pancreatic Cancer

Verastem Oncology reported the acceptance of an abstract that will include initial safety and efficacy results from the RAMP 205 trial of avutometinib and defactinib in combination with current standard of care gemcitabine and nab-paclitaxel in first-line metastatic pancreatic cancer at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
GFH375 (VS-7375): Oral KRAS G12D (ON/OFF) Inhibitor

GenFleet Therapeutics investigational new drug (IND) application for GFH375 (VS-7375) was submitted in China and accepted for review. Expect to begin a Phase 1 trial in China in H2 2024.
Discovery/lead optimization continues for second and third programs with GenFleet collaboration.
Upcoming Presentations

Verastem Oncology reported the acceptance of an abstract for poster presentation at the ASCO (Free ASCO Whitepaper) Annual Meeting being held from May 31 to June 4, 2024, in Chicago, IL.

Title: Avutometinib/defactinib and gemcitabine/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Initial safety and efficacy of phase 1b/2 study (RAMP 205).
Abstract Number: 4140
Date/Time: Saturday, June 1, 2024, 1:30 to 4:30 pm CDT
Corporate Updates

Strengthened the executive leadership team with the appointment of John Hayslip, M.D., to chief medical officer in April 2024.
First Quarter 2024 Financial Results

Verastem Oncology ended the first quarter of 2024 with cash, cash equivalents and investments of $110.1 million.

Total operating expenses for the three months ended March 31, 2024 (the "2024 Quarter") were $28.1 million, compared to $19.3 million for the three months ended March 31, 2023 (the "2023 Quarter").

Research & development expenses for the 2024 Quarter were $17.7 million, compared to $12.0 million for the 2023 Quarter. The increase of $5.7 million, or 47.5%, was primarily related to increased contract research organization costs, increased investigator fees and increased personnel costs, including non-cash stock compensation.

Selling, general & administrative expenses for the 2024 Quarter were $10.4 million, compared to $7.3 million for the 2023 Quarter. The increase of $3.1 million, or 42.5%, was primarily related to additional costs in anticipation of a potential launch of avutometinib and defactinib in LGSOC, increased personnel costs, including non-cash stock compensation, and increased consulting and professional fees.

Net loss for the 2024 Quarter was $33.9 million, or $1.26 per share (basic and diluted), compared to $15.7 million, or $0.94 per share (basic and diluted, each as adjusted for the Company’s reverse stock split) for the 2023 Quarter.

For the 2024 Quarter, non-GAAP adjusted net loss was $26.2 million, or $0.98 per share (diluted) compared to non-GAAP adjusted net loss of $17.8 million, or $1.07 per share (diluted, as adjusted for the Company’s reverse stock split), for the 2023 Quarter. Please refer to the GAAP to non-GAAP Reconciliation attached to this press release.

Use of Non-GAAP Financial Measures

To supplement Verastem Oncology’s condensed consolidated financial statements, which are prepared and presented in accordance with generally accepted accounting principles in the United States (GAAP), the Company uses the following non-GAAP financial measures in this press release: non-GAAP adjusted net loss and non-GAAP net loss per share. These non-GAAP financial measures exclude certain amounts or expenses from the corresponding financial measures determined in accordance with GAAP. Management believes this non-GAAP information is useful for investors, taken in conjunction with the Company’s GAAP financial statements, because it provides greater transparency and period-over- period comparability with respect to the Company’s operating performance and can enhance investors’ ability to identify operating trends in the Company’s business. Management uses these measures, among other factors, to assess and analyze operational results and trends and to make financial and operational decisions. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of the Company’s operating results as reported under GAAP, not in isolation or as a substitute for, or superior to, financial information prepared and presented in accordance with GAAP. In addition, these non-GAAP financial measures are unlikely to be comparable with non-GAAP information provided by other companies. The determination of the amounts that are excluded from non-GAAP financial measures is a matter of management judgment and depends upon, among other factors, the nature of the underlying expense or income amounts. Reconciliations between these non-GAAP financial measures and the most comparable GAAP financial measures for the three months ended March 31, 2024 and 2023 are included in the tables accompanying this press release after the unaudited condensed consolidated financial statements.

About the Avutometinib and Defactinib Combination

Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib, a selective FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.

Verastem Oncology is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. RAMP 301 (NCT06072781) is an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed in each of the dose optimization and expansion phases and the low-dose evaluation.

Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS (sotorasib) in combination with avutometinib and defactinib and KRAZATI (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. The RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award.

About GFH375 (VS-7375)

GFH375 (VS-7375) is a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, identified as the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Upon approval of the investigational new drug (IND) application in China (which is currently under review), GenFleet is expected to initiate a Phase 1 trial in China in the second half of 2024. The collaboration includes three discovery programs, the first being the KRAS G12D inhibitor, and will provide Verastem Oncology with exclusive options to obtain licenses to each of the three compounds in the collaboration after successful completion of pre-determined milestones in Phase 1 trials. The licenses would give Verastem Oncology development and commercialization rights outside of the GenFleet territories of mainland China, Hong Kong, Macau, and Taiwan.

On May 9, 2024 Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) reported financial results for its fiscal 2024 second quarter ended March 31, 2024 (Press release, Arrowhead Pharmaceuticals, MAY 9, 2024, View Source [SID1234643041]). The Company is hosting a conference call today, May 9, 2024, at 4:30 p.m. ET to discuss the results.

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Christopher Anzalone, Ph.D., President and CEO at Arrowhead, said: "Arrowhead has achieved significant progress across our broad pipeline of investigational RNAi-based medicines that leverage the proprietary TRiMTM platform and we continued to strengthen our focus on and investment in our late-stage cardiometabolic programs. As we approach completion of the PALISADE Phase 3 study of plozasiran and initiate additional Phase 3 trials of both plozasiran and zodasiran, we will continue to efficiently execute our clinical studies. Simultaneously, we plan to begin the regulatory submission process, refine our commercial strategy, and build the commercial infrastructure to support it."

Webcast and Conference Call and Details

Investors may access a live audio webcast on the Company’s website at View Source A replay of the webcast will be available approximately two hours after the conclusion of the call.

For analysts that wish to participate in the conference call, please register at https://register.vevent.com/register/BIf9305354ec6b44e3b3e946792a393a5e. Once registered, you will receive the dial-in number and a personalized PIN code that will be required to access the call.

Selected Recent Events

Received a $50 million milestone payment from Royalty Pharma plc, which was paid in the third quarter of fiscal 2024, following the completion of enrollment of the Phase 3 OCEAN(a) – Outcomes Trial of olpasiran, being conducted by Amgen. Olpasiran, a small interfering RNA originally developed by Arrowhead using its proprietary Targeted RNAi Molecule (TRiMTM) platform, is designed to lower levels of lipoprotein(a), a genetically determined risk factor for cardiovascular disease.

Presented final data from the Phase 2 SHASTA-2 study of investigational plozasiran in patients with severe hypertriglyceridemia in a late-breaking oral presentation at the American College of Cardiology 73rd Annual Scientific Session & Expo and simultaneously published in the journal JAMA Cardiology. Key results included the following:
Treatment with plozasiran led to dose-dependent placebo-adjusted reductions in triglycerides (primary endpoint) of -49% (P < 0.001), -53% (P < 0.001), and -57% (P < 0.001), driven by placebo-adjusted reductions in APOC3 of -68% (P < 0.001), -72% (P < 0.001), and -77% (P < 0.001) at week 24, after receiving two doses of 10 mg, 25 mg, and 50 mg plozasiran, respectively. Mean maximum, non-placebo adjusted reductions from baseline in triglycerides and APOC3 were up to 86% and 90% and typically occurred around week 16 or week 20.
Among patients treated with plozasiran, 90.6% achieved a triglyceride level less than 500 mg/dL, the level associated with increased risk of acute pancreatitis, at week 24. In addition, 48.4% of patients achieved normal triglyceride levels of less than 150 mg/dL at week 24.

Subjects treated with plozasiran also showed improvements in multiple atherogenic lipid and lipoprotein levels, including remnant cholesterol, HDL-cholesterol, and non-HDL cholesterol.
Plozasiran demonstrated a favorable safety profile in the SHASTA-2 study. The adverse event and serious adverse event profile were similar across treatment groups. Observed adverse events generally reflected the comorbidities and underlying conditions of the study population.

Initiated an Expanded Access Program (EAP) to make investigational plozasiran available outside of a clinical trial for patients with familial chylomicronemia syndrome (FCS) who meet certain program eligibility criteria.
The plozasiran EAP is for individuals living with FCS. As with any investigational medicine that has not been approved by regulatory authorities, investigational plozasiran may or may not be effective in treating your diagnosis or condition, and there may be risks associated with its use. If you are a patient or caregiver wishing to know more about this plozasiran EAP for FCS, please discuss this EAP and all treatment options with your treating physician. If you are a treating physician and are seeking information about the plozasiran EAP or would like to request access for a patient, please contact [email protected].

Launched the 2024 Summer Series of R&D webinars to highlight specific therapeutic areas in Arrowhead’s pipeline. Each event will feature presentations by Arrowhead team members and external key opinion leaders, who will discuss the respective disease areas and treatment landscapes. 2024 Summer Series Schedule:
May 23, 2024 – Muscular
June 25, 2024 – Cardiometabolic
July 16, 2024 – Pulmonary
August 15, 2024 – Obesity/Metabolic
September 25, 2024 – Central Nervous System
Dosed the first subjects in a Phase 1/2a clinical trial (NCT06209177) of ARO-CFB, designed to reduce hepatic expression of complement factor B, and is being developed as a potential treatment for diseases associated with activation of the complement pathway.
Dosed the first subjects in a Phase 1/2a clinical trial (NCT06138743) of ARO-DM1, designed to reduce expression of the dystrophia myotonica protein kinase gene in the muscle, and is being developed as a potential treatment for type 1 myotonic dystrophy, the most common adult-onset muscular dystrophy.
Strengthened the balance sheet through an underwritten registered offering of common stock for gross proceeds of approximately $450 million, before deducting underwriting discounts, commissions, and other offering expenses payable by the company.
Selected Fiscal 2024 Second Quarter Financial Results

ARROWHEAD PHARMACEUTICALS, INC.
CONSOLIDATED CONDENSED FINANCIAL INFORMATION
(in thousands, except per share amounts)

OPERATING SUMMARY

Three Months Ended

March 31,

2024

2023

(unaudited)

Revenue

$

–

$

146,267

Operating Expenses:

Research and development

101,122

74,881

General and administrative expenses

25,069

23,221

Total operating expenses

126,191

98,102

Operating (loss) income

(126,191

)

48,165

Total other expense

(805

)

(489

)

(Loss) income before income tax expense and noncontrolling interest

(126,996

)

47,676

Income tax expense

–

Net (loss) income including noncontrolling interest

(126,996

)

47,676

Net (loss) income attributable to noncontrolling interest, net of tax

(1,696

)

(999

)

Net (loss) income attributable to Arrowhead Pharmaceuticals, Inc.

$

(125,300

)

$

48,675

Net (loss) income per share attributable to Arrowhead Pharmaceuticals, Inc. – Diluted

$

(1.02

)

$

0.45

Weighted-average shares used in calculating – Diluted

123,285

108,143

FINANCIAL POSITION SUMMARY

March 31, 2024

September 30, 2023

(unaudited)

Cash, cash equivalents and restricted cash

$

127,704

$

110,891

Investments

395,410

292,735

Total cash resources (cash and investments)

523,114

403,626

Other assets

432,036

361,926

Total Assets

$

955,150

$

765,552

Current deferred revenue

$

–

$

866

Other liabilities

459,745

477,524

Total Liabilities

$

459,745

$

478,390

Total Arrowhead Pharmaceuticals, Inc. Stockholders’ Equity

$

483,794

$

271,343

Noncontrolling Interest

11,611

15,819

Total Noncontrolling Interest and Stockholders’ Equity

$

495,405

$

287,162

Total Liabilities, Noncontrolling Interest and Stockholders’ Equity

$

955,150

$

765,552

Shares Outstanding

124,133

107,312