On May 14, 2025 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported the first patient has been dosed in RASolve 301, a global, randomized, open-label Phase 3 clinical trial. RASolve 301 will evaluate the safety and efficacy of daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor, in patients with previously treated, locally advanced or metastatic RAS mutant non-small cell lung cancer (NSCLC) compared to docetaxel chemotherapy (Press release, Revolution Medicines, MAY 14, 2025, View Source [SID1234653079]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

RASolve 301 is anticipated to enroll approximately 420 patients with NSCLC worldwide who have received one to two prior lines of therapy for the treatment of advanced disease including an anti-PD-1/anti-PD(L)-1 agent and platinum-based chemotherapy. The pivotal clinical trial is designed to include a core population of patients with NSCLC carrying RAS mutations at position G12 (G12X), and an expanded population that also includes patients with tumors carrying other specific RAS mutations. The dual primary endpoints are progression-free survival (PFS) and overall survival (OS) in the core patient population. Key secondary endpoints include PFS, OS and objective response rate (ORR) in the expanded population.

"We are pleased that dosing is underway in the RASolve 301 Phase 3 clinical trial, an important step in developing daraxonrasib, a highly innovative compound that targets a diverse array of RAS mutations that drive tumor growth in 30% of NSCLC cases," said Mark A. Goldsmith M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. "For the vast majority of these RAS cancer drivers, there are currently no approved targeted drugs that can be used in place of chemotherapy. In this trial we are collaborating with physicians globally to evaluate the potential of daraxonrasib as a new therapy for people living with RAS mutant lung cancer."

The company’s decision to evaluate daraxonrasib as a monotherapy in this NSCLC setting was informed by early evidence from a single-arm trial showing the compound had an acceptable safety profile and encouraging antitumor activity. Daraxonrasib is also being evaluated in the RASolute 302 clinical trial, which is a global, randomized Phase 3 trial evaluating daraxonrasib versus standard of care chemotherapy in second-line patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC).

About Non-Small Cell Lung Cancer and RAS Mutations
More than 197,000 people are diagnosed with non-small cell lung cancer (NSCLC) in the U.S. each year.1 Despite treatment advancements, NSCLC remains a leading cause of cancer-related mortality worldwide, primarily due to its late-stage diagnosis and limited response to conventional therapies. RAS mutations are among the most common oncogenic drivers in NSCLC, occurring in approximately 30% of cases.2 A significant challenge in treating NSCLC is its genetic diversity, with different mutations including RAS G12X, G13X and Q61X each playing a crucial role in the development and progression of NSCLC in this patient population.

About Daraxonrasib
Daraxonrasib (RMC-6236) is an oral, direct RAS(ON) multi-selective inhibitor with the potential to help address a wide range of cancers driven by oncogenic RAS mutations. Daraxonrasib suppresses RAS signaling by blocking the interaction of RAS(ON) with its downstream effectors. It does so by targeting oncogenic RAS mutations G12X, G13X and Q61X that are common drivers of major cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).

On May 14, 2025 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company utilizing its novel proprietary ARCUS platform to develop in vivo gene editing therapies for diseases with high unmet need, reported the strategic prioritization and acceleration of PBGENE-DMD, the Company’s first-in-class in vivo gene editing approach for Duchenne Muscular Dystrophy (DMD) and highlighted a PBGENE-DMD poster presentation at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting being held May 13-17, 2025, in New Orleans, Louisiana (Press release, Precision Biosciences, MAY 14, 2025, View Source [SID1234653078]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Nomination and acceleration of PBGENE-DMD as our second wholly owned program is a result of the compelling preclinical evidence we have generated to date," said Michael Amoroso, President and Chief Executive Officer of Precision BioSciences. "Currently, there are no approved treatments or treatments in development that significantly improve muscle function over time to beneficially alter the long-term prognosis of this devastating disease. PBGENE-DMD is the first in vivo gene editing program that has the potential to transform the treatment paradigm and deliver durable functional improvement for most patients, as up to 60% of those afflicted carry mutations in the ‘hot spot’ region between exons 45-55. Based on these data, the significant unmet need in DMD and the clear regulatory guidance established for new therapeutics in DMD, we are committed to advancing PBGENE-DMD to the next stage of development. We look forward to rapidly advancing this program toward the clinic as our second wholly owned program after PBGENE-HBV and further establishing the therapeutic potential of ARCUS in vivo gene editing."

DMD is a genetic disease caused by mutations in the dystrophin gene that prevent production of the dystrophin protein and affects approximately 15,000 patients in the U.S. alone. There are currently no approved therapies that can drive significant and durable functional muscle improvements. PBGENE-DMD employs two complementary ARCUS nucleases delivered in a single AAV to excise exons 45-55 of the dystrophin gene with the aim of restoring the body’s natural production of a functional dystrophin protein.

"PBGENE-DMD has the potential to provide a one-time, durable intervention that could allow for lifelong benefits in muscle regeneration and function. Preclinical models have shown that PBGENE-DMD results in significant and sustained improvement of maximum force output by restoring the human body’s production of a functional, near full-length dystrophin protein," added Cassie Gorsuch, Ph.D., Chief Scientific Officer at Precision BioSciences. "Approximately one in every 3,500–5,000 males in the United States is afflicted with DMD, and these patients have limited treatment options. Our prioritization of PBGENE-DMD in conjunction with long term, preclinical functional improvement reinforces our belief in the program and its potential to address significant unmet need for patients living with DMD."

In preclinical data being presented at ASGCT (Free ASGCT Whitepaper), PBGENE-DMD demonstrated significant and durable functional improvement in a humanized DMD mouse model. Following AAV delivery, PBGENE-DMD restored the body’s ability to produce a functional dystrophin protein broadly across multiple muscles, including cardiac and skeletal muscles. Over the course of 9 months, mice treated with PBGENE-DMD showed increased dystrophin protein expression resulting in substantial and sustained functional muscle improvement. In addition, PBGENE-DMD-edited dystrophin mRNA transcript in muscle satellite stem cells, which are progenitor cells for new muscle cells, supports the potential for long-term durability.

"Precision’s ARCUS gene excision approach targeting exons 45-55 represents a novel approach to addressing the underlying disease for the majority of patients with Duchenne muscular dystrophy," said Debra Miller, founder and CEO of CureDuchenne. "We are excited by the potential of this approach and look forward to Precision educating the DMD community about it at our upcoming FUTURES National Conference on May 24." CureDuchenne is a nonprofit organization recognized as the global leader in research, patient care and innovation for improving and extending the lives of those with Duchenne muscular dystrophy.

Precision is working diligently and targeting to file an IND and/or CTA in 2025 with clinical data anticipated in 2026. The Company believes that its current cash runway will be sufficient to progress both PBGENE-HBV, its current Phase 1 clinical program, and PBGENE-DMD through Phase 1 clinical readouts.

In order to accelerate development of PBGENE-DMD and maintain operational capability to pursue PBGENE-HBV and PBGENE-DMD through Phase 1 clinical results, Precision plans to pause development of PBGENE-3243, its potential treatment for m.3243-associated mitochondrial disease, and will stage future development alone or with partners following completion of the Phase 1 ELIMINATE-B trial and after the PBGENE-DMD program enters the clinic. Precision has completed pre-IND discussions with regulators for PBGENE-3243 and the final clinical candidate is ready to commence toxicology studies. "We remain excited about the potential for PBGENE-3243 to help people living with m.3243 mitochondrial diseases and remain committed to those afflicted with m.3243 associated mitochondrial disease in the future, alone or through partnerships," added Mr. Amoroso.

Conference Call Information

Precision BioSciences will host a conference call on Thursday, May 15 at 8:00 am ET. To access the live conference call, participants may register here. The live audio webcast of the call will be available in the Investors section under Events & Presentations at investor.precisionbiosciences.com. An archived replay of the webcast will be available for approximately 30 days following the event.

PBGENE-DMD Presentation Details:

Title: ARCUS-Mediated Gene Editing Excision of Exons 45-55 of the Human Dystrophin Gene using PBGENE-DMD Leads to Functional Dystrophin Protein and Durable Restoration of Skeletal Muscle-Function In Vivo for the Treatment of Duchenne Muscular Dystrophy

Session: Poster Reception

Date and Time: Wednesday, May 14, 2025, 5:30 PM – 7:00 PM CT

Location: Poster Hall I2

On May 14, 2025 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported first quarter 2025 financial results and business updates (Press release, Precigen, MAY 14, 2025, View Source [SID1234653073]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are extremely pleased with the progress of our PRGN-2012 program and its immense potential for RRP patients. We remain laser-focused on advancing the program toward the rapidly approaching PDUFA target action date in August. If approved, PRGN-2012 has the potential to be the first and only FDA-approved therapeutic for the treatment of RRP," said Helen Sabzevari, PhD, President and CEO of Precigen. "We encourage anyone interested in learning more about RRP and hearing directly from RRP patients, caregivers, and the healthcare community supporting them to join Precigen and the Recurrent Respiratory Papillomatosis Foundation for the 2025 International RRP Awareness Day on June 11. Panelists will discuss the patient and caregiver experience with RRP, the significant burden of living with a rare and chronic disease such as RRP, and the challenges of repeated surgeries."

"We completed the first quarter with continued financial discipline while appropriately investing in activities related to the potential launch of PRGN-2012. We ended the quarter with cash, cash equivalents, and investments of $81 million, and we reiterate that our cash runway is expected to take us into 2026, without consideration of product-related revenue from the potential commercial launch of PRGN-2012 later this year," said Harry Thomasian Jr., CFO of Precigen.

Key Program and Company Highlights

2025 International RRP Awareness Day

The Company and the Recurrent Respiratory Papillomatosis Foundation (RRPF) will host the 2025 International RRP Awareness Day on June 11. RRP Awareness Day brings together patients with recurrent respiratory papillomatosis (RRP), their caregivers, and the healthcare community supporting them to encourage dialogue and build community among those affected by this rare, debilitating chronic disease. To stay up-to-date with RRP Awareness Day activities and to register for the June 11 webcast, please visit www.RRPAwareness.org.

PRGN-2012 (nonproprietary name: zopapogene imadenovec†) AdenoVerse Gene Therapy in RRP

PRGN-2012 is an investigational off-the-shelf AdenoVerse gene therapy designed to elicit immune responses directed against cells infected with human papillomavirus (HPV) 6 or HPV 11 for the treatment of adults with RRP. PRGN-2012 received Breakthrough Therapy Designation, Orphan Drug Designation, and an accelerated approval pathway from the US Food and Drug Administration (FDA), and Orphan Drug Designation from the European Commission.

· In February 2025, the FDA accepted the Company’s biologics license application (BLA) for PRGN-2012, and granted priority review of the BLA with a Prescription Drug User Fee Act (PDUFA) target action date set for August 27, 2025. The FDA has indicated that they are not currently planning to hold an advisory committee meeting to discuss the BLA.
· Results from the pivotal clinical study of PRGN-2012 for the treatment of RRP were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and published in The Lancet Respiratory Medicine.
· Pivotal study successfully met its primary safety and pre-specified primary efficacy endpoints.
· PRGN-2012 was well-tolerated with no dose-limiting toxicities and no treatment-related adverse events greater than Grade 2.
· 51% (18 out of 35) of study patients achieved Complete Response, requiring no surgeries after treatment with PRGN-2012. Complete Responses have been durable beyond 12 months with median duration of follow up of 30 months, with some complete responders surgery-free for three years as of the March 20, 2025 data cutoff.

· 86% (30 out of 35) of study patients had a decrease in surgical interventions in the year after PRGN-2012 treatment compared to the year prior to treatment; RRP surgeries reduced from a median of 4 (range: 3-10) pre-treatment to 0 (range: 0-7) post-treatment.
· PRGN-2012 treatment induced HPV 6/11-specific T cell responses in RRP study patients with a significantly greater expansion of peripheral HPV-specific T cells in responders compared with non-responders.
· PRGN-2012 significantly (p < 0.0001) improved anatomical Derkay scores and VHI-10 scores in complete responders.
· Patient enrollment continues to advance in the confirmatory clinical trial of PRGN-2012 in accordance with the guidance from the FDA to initiate the study prior to submission of the BLA.
· The Company continues to rapidly advance its commercial and manufacturing readiness campaign in anticipation of a potential launch in 2025.
· The Company selected EVERSANA, a leading provider of commercialization services to the global life sciences industry, to support launch strategy and commercialization of PRGN-2012 in adults with RRP in the United States. The Company and EVERSANA are developing a targeted go-to-market strategy for PRGN-2012 in preparation for potential approval in August. As part of this strategy, the Company is deploying the first wave of field teams in support of launch readiness preparation.
· Based on an internal analysis derived from review of claims data, the market opportunity for PRGN-2012 in RRP is estimated to be approximately 27,000 adult patients in the United States. More than 125,000 patients are estimated outside of the United States.

PRGN-2009 AdenoVerse Gene Therapy in HPV-associated Cancers

PRGN-2009 is an investigational off-the-shelf AdenoVerse gene therapy designed to activate the immune system to recognize and target HPV-associated cancers.

· PRGN-2009 Phase 2 clinical trials, under a cooperative research and development agreement (CRADA) with the National Cancer Institute (NCI) in recurrent/metastatic cervical cancer and in newly diagnosed HPV-associated oropharyngeal cancer, are ongoing.

PRGN-3006 UltraCAR-T in AML and MDS

PRGN-3006 is an investigational multigenic, autologous chimeric antigen receptor T cell (CAR-T) therapy engineered to simultaneously express a CAR specifically targeting CD33, membrane bound IL-15 (mbIL15), and a safety/kill switch. PRGN-3006 has been granted Orphan Drug Designation in patients with acute myeloid leukemia (AML) and Fast Track Designation in patients with relapsed/refractory (r/r) AML by the FDA.

· The Company has completed enrollment of the Phase 1b trial for PRGN-3006 in AML.

Financial Highlights

· Cash, cash equivalents, and investments totaled $81.0 million as of March 31, 2025
· Cash burn for the quarter ended March 31, 2025 was $16.9 million

First Quarter 2025 Financial Results Compared to Prior Year Period

Total revenues increased $0.3 million, or 26%, compared to the three months ended March 31, 2024. This increase was primarily related to increased volume of products sold and services rendered at Exemplar.

Research and development expenses decreased by $3.8 million, or 27%, compared to the three months ended March 31, 2024. The decrease was primarily due to a $1.8 million decrease in costs associated with ActoBio, including depreciation, amortization, personnel, and other operating costs after the Company closed ActoBio’s operations in late 2024. Additionally, there was a decrease of $1.2 million incurred at contract research organizations and an $0.8 million decrease due to a reduction in the number of Research and Development employees as a result of the Company’s asset prioritization announced in the third quarter of 2024.

SG&A expenses increased by $2.2 million, or 22%, compared to the three months ended March 31, 2024. This increase was primarily associated with PRGN-2012 commercial readiness. This increase was partially offset by a reduction in insurance rates and license and patent fees compared to the three months ended March 31, 2024.

Total other income (expense), net, changed from income of $0.6 million in the three months ended March 31, 2024, to expense of $31.6 million in the three months ended March 31, 2025. This change was primarily driven by the recording of a $32.5 million increase in the fair value of warrant liabilities, which was influenced by an increase in the stock price of Precigen and to a lesser extent, an increase in the liability to account for the additional warrants that will be issued as part of the paid-in-kind dividends related to the Company’s Series A Preferred Stock. This decrease was partially offset by a $0.3 million increase in interest income resulting from increased investment balances.

Net loss was $54.2 million, or $(0.18) per basic and diluted share, compared to net loss of $23.7 million, or $(0.10) per basic and diluted share, in the three months ended March 31, 2024. The non-cash change in the fair value of warrant liabilities of $32.5 million recorded in the three months ended March 31, 2025 reduced basic and diluted earnings per share in that period by $0.11.

On May 14, 2025 PDS Biotechnology Corporation (Nasdaq: PDSB) ("PDS Biotech" or the "Company"), a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers, reported a clinical and corporate update and announced financial results for the first quarter ended March 31, 2025 (Press release, PDS Biotechnology, MAY 14, 2025, View Source [SID1234653072]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The first quarter of 2025 and recent weeks have been productive for PDS Biotech, highlighted by the initiation of our VERSATILE-003 Phase 3 clinical trial evaluating Versamune HPV in recurrent/metastatic ("R/M") HPV16-positive head and neck squamous carcinoma ("HNSCC")," said Frank Bedu-Addo, Ph.D., President and Chief Executive Officer of PDS Biotech. "We are pleased to announce that site activation is progressing, and that Mayo Clinic sites have recently been added to the trial. HPV16-positive HNSCC represents a large, rapidly growing patient population in need of targeted therapies to treat the underlying cause of the cancer, and our Versamune HPV investigational therapy is currently the only targeted therapy in a Phase 3 trial specifically for HPV-16 positive tumors."

Clinical and Corporate Update

•
On April 23, 2025, the Company announced that three abstracts on Versamune HPV (PDS0101) were selected for presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held May 30-June 3, 2025, in Chicago, IL.

•
On May 8, 2025, the Company announced that preclinical efficacy and immune response data with a novel investigational Infectimune based universal flu vaccine were featured in two presentations on universal influenza vaccines, including an oral symposium at the American Association of Immunologists’ IMMUNOLOGY2025 Annual Meeting, held May 3-7, 2025, in Honolulu, Hawaii.

•
On March 13, 2025, the Company announced U.S. Food and Drug Administration ("FDA") clearance of an Investigational New Drug ("IND") application for the combination of Versamune MUC1 and PDS01ADC to treat MUC1-positive unresectable, metastatic colorectal carcinoma in patients who failed previous treatment. The National Cancer Institute ("NCI"), under its Cooperative Research and Development Agreement ("CRADA"), will lead the Phase 1/2 clinical trial evaluating the combination of Versamune MUC1 + PDS01ADC in recurrent/metastatic colorectal cancer.

•
On March 7, 2025, the Company announced the initiation of its VERSATILE-003 Phase 3 trial in HPV16-positive first-line recurrent and/or metastatic HNSCC.

•
Trial is designed to include approximately 350 patients

•
PDS Biotech is aligned with the FDA on the design of the registrational trial and clinical endpoints.

■
Two-arm controlled trial with 2:1 randomization

■
Median overall survival is the primary endpoint

■
Interim readouts included in the study design

•
The Company received FDA Fast Track designation for the combination of Versamune HPV and pembrolizumab in R/M HNSCC.

•
For more information on VERSATILE-003, visit ClinicalTrials.gov (Identifier: NCT06790966).

•
On February 27, 2025, the Company announced that it had entered into securities purchase agreements with new and existing healthcare-focused institutional investors, as well as participation from certain directors of the Company, for the purchase and sale of 7,330,121 shares of its common stock (or common stock equivalents in lieu thereof) and warrants to purchase up to an aggregate of 7,330,121 shares of common stock in a registered direct offering priced at-the-market under Nasdaq rules at a combined purchase price of $1.50 for the institutional investors and $1.66 for certain directors of the Company. Approximately $11 million was funded upon the closing of the offering, and up to an additional $11 million may be funded upon full cash exercise of the warrants.

First Quarter 2025 Financial Results

Reported net loss was approximately $8.5 million, or $0.21 per basic and diluted share, for the three months ended March 31, 2025, compared to $10.6 million, or $0.30 per basic share and diluted share, for the three months ended March 31, 2024. The decrease was due to increased benefit from income taxes and lower operating expenses.

Research and development expenses were $5.8 million for the three months ended March 31, 2025, compared to $6.7 million for the three months ended March 31, 2024. The decrease was primarily due to lower clinical trial expenses.

General and administrative expenses were $3.3 million for the quarter ended March 31, 2025, compared to $3.4 million for the three months ended March 31, 2024.

Total operating expenses were $9.1 million for the quarter ended March 31, 2025, compared to approximately $10.1 million for the three months ended March 31, 2024.

Net interest expenses were $0.6 million compared to approximately $0.5 million for the three months ended March 31, 2024.

The Company’s cash balance as of March 31, 2025 was $40 million, compared to $41.7 million as of December 31, 2024.

Conference Call Details

Date: May 14, 2025
Time: 8:00 a.m. Eastern Time
Dial-in: 1-877-704-4453 (Domestic) or 1-201-389-0920 (International)
Webcast Registration: Click Here
Call MeTM Registration: Click Here (Available 15 minutes prior to call)

On May 14, 2025 Pasithea Therapeutics Corp. (NASDAQ: KTTA) ("Pasithea" or the "Company"), a clinical-stage biotechnology company developing PAS-004, a next-generation macrocyclic MEK inhibitor reported initiation of its Phase 1/1b open label study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of PAS-004, in adult participants with neurofibromatosis type 1 (NF1) with symptomatic and inoperable, incompletely resected, or recurrent plexiform neurofibromas (Press release, Pasithea Therapeutics, MAY 14, 2025, View Source [SID1234653071]). The study will also assess preliminary anti-tumor activity and help determine a recommended dose for subsequent Phase 2 trials. Exploratory objectives include assessing the effects of PAS-004 on cutaneous neurofibromas.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The first active clinical trial site is the Royal North Shore Hospital in Sydney, Australia, which is expected to begin patient enrollment in Q2 2025. Additional clinical trial sites in Australia, South Korea, and the United States are expected to be opened in the coming months.

Pasithea has selected Novotech (Australia) Pty Limited as its clinical research organization (CRO) for this trial. The Company is conducting the study through its wholly owned subsidiary in Australia, Pasithea MacroMEK Pty Ltd, and anticipates eligibility for an Australian R&D Tax Incentive with a cash refund of up to 48.5% of the amount spent annually on eligible R&D activities (trial costs) in Australia.

Dr. Rebecca Brown, M.D., Ph.D. a member of Pasithea’s Scientific Advisory Board and Associate Professor of Neuro Oncology at The University of Alabama at Birmingham commented, "I am pleased to have collaborated with the Pasithea team on the design of a comprehensive dose exploration and expansion study to assess the safety and tolerability of PAS-004 in adult NF1 patients. In addition to testing the effects of PAS-004 on plexiform neurofibromas, exploratory endpoints will also examine the effects of PAS-004 on cutaneous neurofibromas. The safety profile observed to date in advanced cancer patients is encouraging, and I look forward to seeing that profile translate to the NF1 population." Dr. Brown added, "One of the biggest challenges in treating plexiform neurofibromas associated with NF1 is ensuring that patients remain on MEK inhibitor therapy over the long-term. Real-world data shows that a significant proportion of NF1 patients discontinue treatment due to poor tolerability, including high rates of rash and gastrointestinal side effects. PAS-004 is also given as a once daily dose that offers a more convenient regimen than current FDA-approved therapies that are dosed twice a day and which could improve patient compliance."

Dr. Tiago Reis Marques, Pasithea’s Chief Executive Officer, said, "Following our recent financing, including the exercise of certain warrants, Pasithea is now funded to produce initial interim patient data in NF1. The initiation of this clinical trial in NF1, the initial indication we seek FDA marketing approval for, marks an important milestone for Pasithea and for patients living with NF1-related plexiform neurofibromas. Activating our first clinical trial site underscores our commitment to advancing PAS-004 as a potential best-in-class next-generation MEK inhibitor. We are encouraged by the safety and clinical data observed to date in oncology patients and are optimistic that PAS-004’s tolerability profile will extend to the NF1 population. Importantly, our existing cancer data has enabled us to begin the NF1 trial at a higher dose than originally contemplated. In addition, we anticipate meaningful cash rebates of eligible trial costs through the Australian R&D Tax Incentive, further enhancing the efficiency of this program."

About the Phase 1/1b Clinical Trial in Adult NF1 Patients

The primary objective of the Phase 1/1b study (NCT06961565) is to evaluate the safety and tolerability of PAS-004 when administered for one 28-day treatment cycle in adult NF1 participants with at least one and up to two additional target plexiform neurofibromas (PNs) that are symptomatic and inoperable, incompletely resected, or recurrent. Secondary objectives are (i) to identify the recommended Part B dose ("RPBD") or Maximum Tolerated Dose (MTD) of PAS-004, (ii) to characterize the PK and PD profile of PAS-004, (iii) to evaluate the preliminary efficacy of PAS-004 on target PN volume, (iv) to evaluate the preliminary efficacy of PAS-004 on the size, appearance, and associated symptoms of cutaneous neurofibromas (CNs), and (v) to evaluate the impact of PAS-004 on quality of life ("QOL") and any physical symptoms attributed to the target PN. Experimental objectives are (i) to evaluate the impact of PAS-004 on QOL and any physical symptoms attributed to CNs, (ii) to evaluate the impact of PAS-004 on pain and function attributed to PNs, and (iii) to investigate PAS-004 effects on CN tumor cellular and molecular biology.

The trial will be conducted in two parts. In Part A, following a screening period of up to 28 days, up to 24 eligible participants will be enrolled sequentially to receive one of four planned dose levels of PAS-004 tablets (4mg, 8mg, 12 mg, 18mg) in a modified 3+3 design. Part A will identify the recommended RPBD. During Part B, up to 24 eligible participants will be enrolled in parallel to receive one of two planned dose levels of PAS-004 tablets. Participants will be dosed at the RPBD level and at a dose level below the RPBD for up to six continuous 28-day treatment cycles. Part B will identify the recommended phase 2 dose (RP2D).

The study is planned to be conducted at five clinical trial sites in Australia, South Korea and the U.S.

To learn more about the PAS-004 clinical trial in adults with NF1-associated plexiform neurofibromas, please visit www.clinicaltrials.gov.