On August 8, 2024 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and reported financial results for the second quarter ended June 30, 2024 (Press release, Xilio Therapeutics, AUG 8, 2024, View Source [SID1234645629]).

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"This quarter, we continued to make meaningful progress advancing our clinical-stage pipeline toward key data milestones and potential value drivers anticipated later this year," said René Russo, Pharm.D., president and chief executive officer of Xilio. "We recently initiated enrollment in our Phase 2 trial of XTX101 in combination with atezolizumab in patients with MSS CRC and our Phase 1 monotherapy dose expansion for XTX301 in patients with advanced solid tumors, and we look forward to reporting clinical data for each of these programs in the fourth quarter. Beyond our clinical-stage pipeline, we are also advancing multiple research-stage programs leveraging our tumor-activated approach for masked immune cell engagers."

Dr. Russo continued, "I am excited to announce the promotion of Chris Frankenfield to chief financial officer of Xilio. Chris’ strategic, financial and operational expertise, together with his collaborative approach and experience building companies, will be instrumental in advancing our pipeline of novel tumor-activated immuno-oncology therapies."

Pipeline and Business Updates

XTX101: tumor-activated anti-CTLA-4

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 designed to block CTLA-4 and deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME).

● Xilio reported the initiation of enrollment in its Phase 2 clinical trial of XTX101 in combination with atezolizumab in patients with MSS CRC, including patients with and without liver metastases. The trial will evaluate the safety and efficacy of XTX101 at 100 mg every six weeks (Q6W) in combination with atezolizumab at 1200 mg every three weeks (Q3W).
● Xilio expects to report initial Phase 2 data for XTX101 in combination with atezolizumab in approximately 20 patients with MSS CRC in the fourth quarter of 2024 and in approximately 20 additional patients (40 patients total) in the first quarter of 2025.

XTX301: tumor-activated, engineered IL-12

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state.

● Xilio reported the initiation of enrollment in Phase 1B monotherapy dose expansion of its ongoing Phase 1 clinical trial of XTX301 in patients with advanced solid tumors. In addition, enrollment in monotherapy dose escalation for XTX301 is ongoing, with XTX301 currently being evaluated at a dose level of 60 ug/kg Q6W (preceded by a single priming dose of 15 ug/kg). To date, XTX301 has been generally well-tolerated, with no dose-limiting toxicities observed in patients.
● Xilio expects to report safety, pharmacokinetic and pharmacodynamic data from the ongoing Phase 1 clinical trial for XTX301 in the fourth quarter of 2024.

Tumor-activated bispecific and immune cell engager programs

● Xilio is advancing a pipeline of research-stage tumor-activated bispecifics and immune cell engagers, including tumor-activated cell engagers and tumor-activated effector-enhanced cell engagers, leveraging the company’s masking technology.

Corporate Updates

● Xilio reported the promotion of Chris Frankenfield to chief financial officer. Mr. Frankenfield will also continue to serve in his current role as chief operating officer.
● In June 2024, Xilio announced the appointments of Aoife Brennan, M.D., and James Shannon, M.D., to its board of directors.

Second Quarter 2024 Financial Results

● Cash Position: Cash and cash equivalents were $74.9 million as of June 30, 2024, compared to $44.7 million as of December 31, 2023. Cash and cash equivalents as of June 30, 2024 included the $30.0 million upfront payment under the company’s license agreement with Gilead Sciences, Inc. (Gilead) for XTX301, approximately $28.1 million in gross proceeds from the sale and issuance of common stock and prefunded warrants to certain existing accredited investors and Gilead in private placements and $7.0 million in gross proceeds from the sale and issuance of common stock under the company’s at-the-market offering program.
● License Revenue: License revenue was $2.4 million for the quarter ended June 30, 2024, which was associated with revenue recognized under the license agreement and stock purchase agreement with Gilead. No license revenue was recognized prior to the quarter ended June 30, 2024.
● Research & Development (R&D) Expenses: R&D expenses were $11.2 million for the quarter ended June 30, 2024, compared to $13.2 million for the quarter ended June 30, 2023. The decrease was primarily driven by decreased manufacturing activities for XTX301, decreased clinical development activities for XTX202, decreased spending related to early-stage programs and indirect research and development costs and decreased personnel-related costs, partially offset by a $1.0 million development milestone payment to WuXi Biologics (Hong Kong) Limited under the company’s CTLA-4 monoclonal antibody license agreement, and increased clinical development activities for XTX101 and XTX301.

● General & Administrative (G&A) Expenses: G&A expenses were $5.8 million for the quarter ended June 30, 2024, compared to $6.9 million for the quarter ended June 30, 2023. The decrease was primarily driven by decreased personnel-related costs, decreased professional and consulting fees, lower costs related to directors’ and officers’ liability insurance and a reduction in other general and administrative expenses.
● Net Loss: Net loss was $13.9 million for the quarter ended June 30, 2024, compared to $19.4 million for the quarter ended June 30, 2023.
Financial Guidance

Based on its current operating plans, Xilio anticipates that its existing cash and cash equivalents as of June 30, 2024 will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2025.

About XTX101 (anti-CTLA-4) and the Phase 1/2 Combination Clinical Trial

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated (unmasked) in the tumor microenvironment. In the third quarter of 2023, Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate XTX101 in combination with atezolizumab (Tecentriq) in a multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety and efficacy of the combination in a Phase 2 clinical trial in patients with microsatellite stable colorectal cancer. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

About XTX301 (IL-12) and the Phase 1 Clinical Trial

XTX301 is an investigational tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment of poorly immunogenic "cold" tumors towards an inflamed or "hot" state. In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences, Inc. for Xilio’s tumor-activated IL-12 program, including XTX301. Xilio is currently evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors in a first-in-human, multi-center, open-label Phase 1 clinical trial. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

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.