On August 8, 2024 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for ziftomenib, the Company’s potent and selective menin inhibitor, for the treatment of advanced gastrointestinal stromal tumors (GIST) (Press release, Kura Oncology, AUG 8, 2024, View Source [SID1234645559]). The Company plans to initiate a Phase 1 first-in-human study of ziftomenib in combination with imatinib, a targeted therapy approved for the treatment of GIST, in early 2025.

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"This important milestone represents the first IND clearance of a menin inhibitor to treat GIST, a solid tumor indication with limited treatment options for patients with advanced disease," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "Although imatinib is utilized in frontline GIST patients, many eventually develop resistance. Our preclinical data suggest ziftomenib has potential to resensitize patients to imatinib and induce deep, durable responses. We look forward to presenting the preclinical data for the combination at an upcoming scientific meeting and initiating a proof-of-concept clinical study early next year."

GIST is the most common form of sarcoma, characterized as KIT-dependent solid tumors. KIT inhibitors are associated with favorable outcomes for patients with GIST, and imatinib is the standard of care in this patient population. For patients who progress on imatinib, subsequent treatment options include other KIT inhibitors; however, these options are limited by moderate efficacy and challenging tolerability. The menin-MLL complex regulates KIT expression in GIST cells, and menin inhibitors display additive therapeutic activity with imatinib in imatinib-sensitive GIST models1. Preclinical data in imatinib-resistant PDX models suggest that ziftomenib in combination with imatinib has the potential to resensitize patients to imatinib and induce durable responses. Kura plans to initiate a proof-of-concept study evaluating ziftomenib in combination with imatinib in patients with advanced GIST after imatinib failure.

On August 8, 2024 Flamingo Therapeutics ("Flamingo") reported that the PEMDA-HN trial has expanded beyond the United States into the UK and Korea (Press release, Flamingo Therapeutics, AUG 8, 2024, View Source;utm_medium=rss&utm_campaign=flamingo-therapeutics-announces-first-patients-dosed-in-the-united-kingdom-and-korea-in-ongoing-phase-ii-pemda-hn-study-for-head-and-neck-squamous-cell-carcinoma-hnscc [SID1234645597]).

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Patient enrollment in the USA started in February 2024 and now the first patients have been dosed in these new geographies. The PEMDA-HN trial is evaluating danvatirsen in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).

Flamingo’s lead oncology program, danvatirsen, is an antisense oligonucleotide discovered by Ionis that selectively targets STAT3 and has shown clinical activity in HNSCC.

"HNSCC is a difficult-to-treat cancer, with approximately 890,000 new cases each year globally, and accounts for almost 5% of global cancer deaths. Patients are in need of new therapies and we are pleased to have expanded our study beyond the United States," said Andrew Denker, MD PhD, CMO of Flamingo. "This is a significant milestone in the advancement of the PEMDA-HN study, and we are thankful for the support of our study participants, their families and our global collaborators."

Dr. Kevin Harrington, Consultant Oncologist at The Royal Marsden NHS Foundation Trust and Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, commented, "STAT3 blocking using Flamingo’s investigational therapy, danvatirsen, is a potential novel approach to help patients with HNSCC in my clinic. I am pleased that my patients have an opportunity to participate in the PEMDA-HN trial, which I believe may greatly benefit the global oncology field."

PEMDA-HN (NCT05814666) is a multicenter, open-label, randomized study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic HNSCC whose tumor expresses PD-L1. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone. The primary endpoint of the study is to determine the overall response rate by RECIST 1.1 as assessed by the investigator. The secondary endpoints will include safety, duration of response, disease control rate, progression free survival and overall survival. More information on PEMDA-HN can be found here.

On August 8, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the discontinuation of the Phase 3 KeyVibe-008 trial based on the recommendation of an independent Data Monitoring Committee (DMC) (Press release, Merck & Co, AUG 8, 2024, View Source [SID1234645614]). The trial is evaluating the investigational fixed-dose combination (coformulation) of vibostolimab, an anti-TIGIT antibody, and pembrolizumab (KEYTRUDA), Merck’s anti-PD-1 therapy, in combination with chemotherapy compared to atezolizumab in combination with chemotherapy, for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). At a pre-planned analysis, data showed that the primary endpoint of overall survival (OS) met the pre-specified futility criteria. Additionally, when compared to patients in the control arm, patients in the vibostolimab and pembrolizumab fixed-dose combination arm experienced a higher rate of adverse events (AEs) and immune-related AEs. A comprehensive analysis of this study is ongoing.

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Merck is notifying study investigators of the decision and that patients should stop ongoing treatment with the fixed-dose combination of vibostolimab and pembrolizumab and be offered the option to be treated with atezolizumab. Results will be shared with the scientific community.

"Small cell lung cancer remains a difficult disease to treat, as evident by the seven percent five-year survival rate and limited advancements in treatment options," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "Innovative research plays a critical role in improving our understanding to help patients achieve better outcomes, and while we hoped the results would be different, we remain committed to investigating novel approaches to treat this debilitating disease. We are extremely grateful to all of the patients, caregivers and investigators for their participation in this study."

Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations.

In SCLC, Merck and Daiichi Sankyo recently announced that the first patient has been dosed in the IDeate-Lung02 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) in patients with relapsed SCLC versus treatment of physician’s choice of chemotherapy. Merck and Daiichi Sankyo also expanded their existing global co-development and co-commercialization agreement for three investigational DXd antibody-drug conjugates to include Merck’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager that is currently being evaluated in a Phase 1/2 clinical trial (NCT04471727). The companies are planning to evaluate MK-6070 in combination with I-DXd in certain patients with SCLC, as well as other potential combinations. Merck obtained MK-6070 through its acquisition of Harpoon Therapeutics.

Ongoing Phase 3 studies evaluating the vibostolimab and pembrolizumab fixed-dose combination in lung cancer, which are routinely monitored by external data monitoring committees, include KeyVibe-003, KeyVibe-006 and KeyVibe-007. Interim external data monitoring committee safety reviews have not resulted in any study modifications to date and the studies are undergoing ongoing comprehensive safety monitoring.

About KeyVibe-008

KeyVibe-008 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT05224141) evaluating a fixed-dose combination of vibostolimab and pembrolizumab (MK-7684A) in combination with etoposide and platinum chemotherapy followed by the vibostolimab and pembrolizumab fixed-dose combination versus atezolizumab in combination with etoposide and platinum chemotherapy followed by atezolizumab for the first-line treatment of patients with ES-SCLC. The primary endpoint is OS, and key secondary endpoints include progression-free survival, objective response rate, duration of response, all as assessed by blinded independent central review (BICR). The trial enrolled 460 patients who were randomized (1:1) to receive:

Vibostolimab/pembrolizumab fixed-dose combination (pembrolizumab 200 mg and vibostolimab 200 mg intravenously [IV] every three weeks [Q3W] for four cycles) in combination with etoposide and platinum chemotherapy (carboplatin or cisplatin) Q3W for a total of approximately 12 weeks followed by additional cycles of the vibostolimab/pembrolizumab fixed-dose combination until any of the conditions for discontinuation are met; or
Atezolizumab (1,200 mg Q3W) in combination with etoposide and platinum chemotherapy (carboplatin or cisplatin) Q3W for a total of approximately 12 weeks followed by additional cycles of atezolizumab until any of the conditions for discontinuation are met.
About lung cancer

Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.48 million new cases and 1.8 million deaths from lung cancer globally. In 2024, the overall five-year survival rate for patients diagnosed with lung cancer is 25% in the United States. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. The two main types of lung cancer are non-small cell and small cell. Small cell lung cancer accounts for about 15% of all lung cancers. Patients with small cell lung cancer have a particularly poor prognosis, with an estimated five-year survival rate of 7% for patients in the United States with any stage of the disease. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced.

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.