On May 23, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of a conditional marketing authorization for mirdametinib, a MEK inhibitor, for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above (Press release, SpringWorks Therapeutics, MAY 23, 2025, View Source [SID1234653361]). The European Commission (EC) will review the CHMP opinion and is expected to make a final decision regarding the approval in the third quarter of 2025. If approved, mirdametinib will be available in 1 and 2 mg capsules and in a 1 mg dispersible tablet, which dissolves easily in water.

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"The positive opinion from the CHMP brings us one step closer to delivering our medicine to both children and adults with NF1-PN in Europe, who we believe are in need of new therapeutic advances," said Saqib Islam, Chief Executive Officer of SpringWorks. "Upon approval, we look forward to bringing mirdametinib to appropriate patients in Europe as quickly as possible."

NF1 is a genetic disorder that affects approximately 3 in 10,000 people in the EU, or an estimated 135,000 people.1,2 Patients with NF1 have approximately a 30 to 50% lifetime risk of developing plexiform neurofibromas, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment.3,4​ Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, an aggressive and potentially fatal disease.5 Surgical removal can be challenging due to the infiltrative tumor growth pattern of plexiform neurofibromas along nerves, and up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.6,7,8

"NF1-PN is a genetic disorder that can be highly morbid and unpredictable. It takes a significant physical and emotional toll on patients and their caregivers, and there have been limited treatment options available," said Ignacio Blanco, MD, PhD, Chairman of the National Reference Center for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias i Pujol, Spain. "Surgical removal of plexiform neurofibromas can be challenging and is often not possible, so if approved, mirdametinib could be an important treatment option for children and adult patients in Europe."

The CHMP opinion was based on the Marketing Authorization Application (MAA) for mirdametinib, which was validated by the EMA in August 2024. The MAA centered on the primary results from the Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN age 2 years or older (58 adults and 56 pediatric patients). The study met the primary endpoint of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating an ORR of 41% (N= 24/58) in adults and 52% in children (N=29/56). The median best percentage change in target PN volume was -41% (range: -90 to 13%) in adults and -42% (range: -91 to 48%) in children. Among those with a confirmed response, 88% percent of adults and 90% of children had a response of at least 12 months duration, and 50% and 48%, respectively, had a response of at least 24 months duration. Both adults and children also experienced early and sustained significant improvements from baseline in pain and quality of life as assessed across multiple patient-reported outcome tools.9

Mirdametinib demonstrated a manageable safety and tolerability profile. The most common adverse events (>25%) reported in adults receiving mirdametinib were rash, diarrhea, nausea, musculoskeletal pain, vomiting and fatigue. The most common adverse events (>25%) occurring in children were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction and nausea.9

Mirdametinib is approved in the U.S. for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

About the ReNeu Trial
ReNeu (NCT03962543) is an ongoing, multi-center, open-label, single arm, Phase 2b trial evaluating the efficacy, safety and tolerability of mirdametinib in patients ≥2 years of age with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint is confirmed objective response rate (ORR) defined as the proportion of patients with a ≥20% reduction in target tumor volume on consecutive scans during the 24-cycle treatment phase, as measured by MRI and assessed by blinded independent central review. Secondary endpoints include safety and tolerability, duration of response, and changes in patient-reported outcomes from baseline to Cycle 13. The treatment phase of the trial is complete, and results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Patients who completed the treatment phase were eligible to continue receiving treatment in the optional long-term follow-up portion of the study, which is ongoing.

About NF1-PN
Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.10,11 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals.3,12 In the EU, NF1 affects approximately 3 in 10,000 people, or an estimated 135,000 people.1,2 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.13 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.1

NF patients have approximately a 30%-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.3,4,5 NF1-PNs are most often diagnosed in the first two decades of life.3 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.14,15

Surgical removal of these tumors can be challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.5 Up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.6,7,8

About Mirdametinib
Mirdametinib is an oral, small molecule MEK inhibitor approved in the United States for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.

The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1.

On May 23, 2025 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company focused on enhancing the standard of care for bevacizumab for the treatment of retina diseases, reported the pricing of an underwritten public offering of 9,285,714 shares of its common stock, together with accompanying warrants to purchase 18,571,428 shares of its common stock (Press release, Outlook Therapeutics, MAY 23, 2025, View Source [SID1234653360]). The combined public offering price of common stock and accompanying warrant is $1.40. The common stock is being sold in combination with an accompanying warrant to purchase two shares of common stock issued for each share of common stock sold. The accompanying warrant has an exercise price of $1.40 per share, will become exercisable immediately and will expire five years from the date of issuance. The offering is expected to close on May 27, 2025, subject to the satisfaction of customary closing conditions.

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The gross proceeds from the offering, before deducting the underwriting discounts and commissions and offering expenses payable by Outlook Therapeutics are expected to be approximately $13.0 million. Outlook Therapeutics intends to use the net proceeds from the offering for working capital and other general corporate purposes.

BTIG, LLC is acting as sole book-running manager for the offering.

The securities described above are being offered by Outlook Therapeutics pursuant to a shelf registration statement on Form S-3 (No. 333-278340) that was declared effective by the Securities and Exchange Commission (SEC) on April 5, 2024. A preliminary prospectus supplement and accompanying prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. Copies of the preliminary prospectus supplement and the final prospectus supplement relating to this offering may be obtained, when available, by contacting: BTIG, LLC, 65 East 55th Street, New York, New York 10022, by telephone at (212) 593-7555 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that state or jurisdiction.

On May 23, 2025 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, reported new data from the Phase I/II GOBLET clinical trial in a poster presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Oncolytics Biotech, MAY 23, 2025, View Source [SID1234653359]). The presentation highlights pelareorep’s mechanism of action in pancreatic ductal adenocarcinoma (PDAC), offering new insights into how this immunotherapy stimulates multiple arms of the immune system and primes tumors for treatment.

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"For the first time, we’re able to map the cascade of immune responses stimulated by pelareorep," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer for Oncolytics Biotech. "It starts with the expansion of anti-reovirus T cells, followed by the upregulation of chemokines that mediate the expansion of pre-existing TIL clones in the blood. These T cells can now return to the tumor and attack it, resulting in a reduction in tumor size. Pelareorep-mediated upregulation of chemokines also makes the tumor microenvironment immunologically active and able to actively recruit cancer-specific T cells to the tumor. These findings deepen our understanding of pelareorep’s ability to convert immunologically cold tumors into immunologically active ones that may benefit from pelareorep-based combination therapy."

Abstract Number: 2562
Title: Role of pelareorep in activating anti-tumor immunity in PDAC.
Presentation Type: Poster
Session Title: Developmental Therapeutics – Immunotherapy
Session Date and Time: June 2, 2025, 1:30 – 4:30 p.m. CT

A copy of the ASCO (Free ASCO Whitepaper) presentation will be available on the Media page of Oncolytics’ website (LINK) following the conclusion of the meeting.

Highlights from the poster and abstract include:
•Pelareorep initiates the expansion of reovirus-specific T cells that are associated with favorable clinical responses at week 24
•Pelareorep increases cytokines and chemokines associated with altering the TME to allow anti-viral and anti-tumor T cells to attack the tumor
•The presence of TIL clones in the blood before treatment and the expansion of these clones in the blood post-treatment are associated with favorable clinical responses
•Previously reported efficacy results from GOBLET Cohort 1, which is evaluating the therapeutic regimen of pelareorep, nab-paclitaxel, gemcitabine, and atezolizumab (Tecentriq) in first-line metastatic PDAC patients, showed a 62% overall response rate, an 85% disease control rate, and a 45% 12-month survival rate

About GOBLET
The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 17 centers in Germany and is being managed by AIO-Studien-gGmbH. The primary endpoints of the study are objective response rate (ORR) and/or disease control rate assessed at week 16 and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers. The study comprises five treatment groups:

1.Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line advanced/metastatic pancreatic cancer patients;

2.Pelareorep in combination with atezolizumab in 1st line MSI (microsatellite instability)-high metastatic colorectal cancer patients;

3.Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients

4.Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients; and

5.Pelareorep in combination with modified FOLFIRINOX with and without atezolizumab in newly diagnosed metastatic PDAC patients.

Any cohort meeting pre-specified efficacy criteria in Stage 1 may be advanced to Stage 2 and enroll additional patients.

On May 23, 2025 Instil Bio, Inc. (Nasdaq: TIL, "Instil") and ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (HKEX Code: 1541.HK, "ImmuneOnco"), reported that they will jointly host an investor and research analyst breakfast in Chicago, Illinois on Saturday, May 31, 2025 at 8:00 to 9:30 am CT adjacent to the McCormick Convention Center (Press release, Instil Bio, MAY 23, 2025, View Source [SID1234653358]).

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Instil and ImmuneOnco management, along with a key opinion leader in the field of immuno-oncology, will discuss the evolving PD-(L)1xVEGF bispecific antibody landscape and recent clinical trial updates from Instil and ImmuneOnco.

Investors and analysts interested in attending should register by emailing their contact information to reserve seating to [email protected].

On May 23, 2025 IMUNON, Inc. (NASDAQ: IMNN), a clinical-stage company in Phase 3 development of its DNA-mediated immunotherapy, reported new positive data from the Company’s Phase 2 OVATION 2 Study of IMNN-001, an investigational therapy for the treatment of advanced ovarian cancer. Results are being highlighted in an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held May 30 – June 3, 2025, in Chicago, Illinois and virtually, and are also being published simultaneously in the peer-reviewed journal Gynecologic Oncology (Press release, IMUNON, MAY 23, 2025, View Source [SID1234653357]).

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Based on the highly encouraging Phase 2 OVATION 2 Study results and following alignment with the U.S. Food and Drug Administration (FDA), IMUNON recently initiated the first two sites for its pivotal Phase 3 OVATION 3 Study of IMNN-001 in newly diagnosed advanced ovarian cancer.

"We are very encouraged by these remarkable results and the fact that they are being presented in two of the most prestigious platforms in oncology research – the ASCO (Free ASCO Whitepaper) Annual Meeting and Gynecologic Oncology," said Stacy Lindborg, Ph.D., president and chief executive officer of IMUNON. "As we continue to evaluate findings from our Phase 2 OVATION 2 Study, the data show consistently strong improvement in overall and progression-free survival, suggesting that IMNN-001 may drive positive outcomes that can truly make a difference in the lives of women with ovarian cancer, even for those with advanced and very difficult to treat stages of disease."

"The results from this Phase 2 trial are powerful and highly encouraging. Typically, an increase in survival of six months is considered clinically meaningful. The data being presented at ASCO (Free ASCO Whitepaper) indicate that IMNN-001 could extend the lives of women with newly diagnosed with advanced ovarian cancer by one year or longer, representing a potentially historic advance in standard of care," said Premal H. Thaker, M.D., Interim Chief of Gynecologic Oncology, David & Lynn Mutch Distinguished Professor of Obstetrics & Gynecology, Director of Gynecologic Oncology Clinical Research at Washington University School of Medicine, OVATION 2 Study Chair and Study Chair of Phase 3 OVATION 3 trial. "This is the first immunotherapy with a favorable safety profile to demonstrate survival benefits when used in conjunction with standard of care chemotherapy in a frontline setting. The fact that IMNN-001 has the potential to be used in conjunction with PARP inhibitors and in women with HRD and BRCA mutations is also particularly exciting. I look forward to helping enroll the Phase 3 trial in the months ahead."

Participants with newly diagnosed advanced epithelial ovarian cancer in the Phase 2 OVATION 2 Study (n=112) were randomized 1:1 to evaluate the safety and efficacy of IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (N/ACT) compared to standard of care (SoC) N/ACT alone, with a median follow-up of 31 months. Among the findings being presented at the ASCO (Free ASCO Whitepaper) Annual Meeting:

Patients in the intent-to-treat (ITT) population administered IMNN-001 plus SoC N/ACT achieved a median increase in overall survival (OS) of 13 months compared to SoC N/ACT alone (46 vs. 33 months), with a hazard ratio of 0.69.
Increased therapeutic activity was observed among patients treated with poly ADP-ribose polymerase (PARP) inhibitors as part of standard maintenance therapy, with the median OS not yet reached in the IMNN-001 treatment arm after more than five years (vs. 37 months in the control arm), with a hazard ratio of 0.38.
Increased therapeutic activity was also observed in women positive for homologous recombination deficiency (HRD+), including BRCA1 or BRCA2 mutations, with a hazard ratio of 0.42.
For the ITT population, patients treated with IMNN-001 plus SoC N/ACT achieved a median 3-month increase in progression-free survival (PFS) compared to SoC N/ACT alone (14.9 vs. 11.9 months), with a hazard ratio of 0.79.
Patients also receiving PARP inhibitors achieved a median 11.7-month increase in PFS when treated with IMNN-001 and SoC N/ACT compared to SoC N/ACT alone (33.8 vs. 22.1 months), with a hazard ratio of 0.8.
IMNN-001 was well tolerated, with the most common adverse events (AEs) primarily including abdominal pain, nausea and vomiting. There were no reports of cytokine release syndrome, systemic toxicity or serious immune-related AEs.
The details of the ASCO (Free ASCO Whitepaper) oral presentation are as follows:

Abstract Title: A phase I/II study of the safety and efficacy of intraperitoneal IMNN-001 in combination with neoadjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian cancer (EOC): Updated survival analysis from OVATION-2 trial.
Presenting Author: Premal H. Thaker, M.D., Washington University School of Medicine, OVATION 2 Study Chair
Date: Tuesday, June 3, 2025
Session Time: 8:00-9:30 a.m. CT
Session Title: Gynecologic Cancer
Abstract Number: 5516
"These data also further validate our TheraPlas technology platform on which IMNN-001 is based and its potential to harness the powerful immunological properties of IL-12 to target the tumor micro-environment and treat ovarian cancer effectively, while alleviating side effects often seen with other immunotherapies. We look forward to advancing our Phase 3 pivotal trial of IMNN-001 as quickly as possible in efforts to bring this novel therapy to the many women in desperate need of new treatment options," added Dr. Lindborg.

In the pivotal Phase 3 OVATION 3 Study of IMNN-001, study participants will be randomized 1:1 and include women with newly diagnosed advanced ovarian cancer (stage IIIC or IV) who are eligible for N/ACT (the ITT population), with a sub-group of HRD+ women including those with BRCA1 or BRCA2 mutations. The primary endpoint of the study is OS, and secondary endpoints are surgical response score, chemotherapy response score, clinical response and time to second-line treatment. The study will also assess several exploratory endpoints.

About the Phase 2 OVATION 2 Study

OVATION 2 evaluated the dosing, safety, efficacy and biological activity of intraperitoneal administration of IMNN-001 in combination with neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin in patients newly diagnosed with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Treatment in the neoadjuvant period is designed to shrink the tumors as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT, patients undergo interval debulking surgery, followed by three additional cycles of adjuvant chemotherapy to treat any residual tumor. This open-label study enrolled 112 patients who were randomized 1:1 and evaluated for safety and efficacy to compare NACT plus IMNN-001 versus standard-of-care NACT. In accordance with the study protocol, patients randomized to the IMNN-001 treatment arm could receive up to 17 weekly doses of 100 mg/m2 in addition to NACT. As a Phase 2 study, OVATION 2 was not powered for statistical significance. Additional endpoints included objective response rate, chemotherapy response score and surgical response.

About IMNN-001 Immunotherapy

Designed using IMUNON’s proprietary TheraPlas platform technology, IMNN-001 is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system that enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer cell proliferation. IMUNON previously reported positive safety and encouraging Phase 1 results with IMNN-001 administered as monotherapy or as combination therapy in patients with advanced peritoneally metastasized primary or recurrent ovarian cancer and completed a Phase 1b dose-escalation trial (the OVATION 1 Study) of IMNN-001 in combination with carboplatin and paclitaxel in patients with newly diagnosed ovarian cancer. IMUNON previously reported positive results from the recently completed Phase 2 OVATION 2 Study, which assessed IMNN-001 (100 mg/m2 administered intraperitoneally weekly) plus neoadjuvant and adjuvant chemotherapy (NACT) of paclitaxel and carboplatin compared to standard-of-care NACT alone in 112 patients with newly diagnosed advanced ovarian cancer.

About Epithelial Ovarian Cancer

Epithelial ovarian cancer is the sixth deadliest malignancy among women in the U.S. There are approximately 20,000 new cases of ovarian cancer every year and approximately 70% are diagnosed in advanced Stage III/IV. Epithelial ovarian cancer is characterized by dissemination of tumors in the peritoneal cavity with a high risk of recurrence (75%, Stage III/IV) after surgery and chemotherapy. Since the five-year survival rates of patients with Stage III/IV disease at diagnosis are poor (41% and 20%, respectively), there remains a need for a therapy that not only reduces the recurrence rate, but also improves overall survival. The peritoneal cavity of advanced ovarian cancer patients contains the primary tumor environment and is an attractive target for a regional approach to immune modulation.