On January 8, 2025 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the National Medical Products Administration (NMPA) of China approved GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] for use in males 9-26 years of age to help prevent certain HPV-related cancers and diseases (Press release, Merck & Co, JAN 8, 2025, View Source [SID1234649506]). The approval makes GARDASIL the first HPV vaccine approved for use in males in China. GARDASIL is now indicated in China to prevent anal cancers caused by HPV Types 16 and 18, genital warts (condyloma acuminata) caused by HPV Types 6 and 11, and the following precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, and 18: grade 1, grade 2, and grade 3 anal intraepithelial neoplasia (AIN).

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"The approval of GARDASIL for use in males 9-26 years old in China is a significant step forward in advancing public health," said Joseph Romanelli, president, Human Health International, Merck. "Since first approval, our HPV vaccines have helped protect over 50 million females in China from certain HPV-related cancers and diseases. With this expanded approval, we look forward to helping protect this new population of Chinese males from certain HPV-related cancers and diseases."

Indications for GARDASIL1

GARDASIL is a vaccine indicated in females 9 through 45 years of age. GARDASIL is indicated for the prevention of cervical, vulvar, vaginal, and anal cancers caused by HPV Types 16 and 18, precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, and 18, and for the prevention of genital warts caused by HPV Types 6 and 11.

GARDASIL is indicated in males 9 through 26 years of age. GARDASIL is indicated for the prevention of anal cancer caused by HPV Types 16 and 18, and precancerous or dysplastic lesions caused by HPV Types 6, 11, 16, and 18, and for the prevention of genital warts caused by HPV Types 6 and 11.

GARDASIL does not eliminate the necessity for vaccine recipients to undergo screening for cervical, vulvar, vaginal, and anal cancers as recommended by a health care provider.

GARDASIL has not been demonstrated to provide protection against diseases caused by:

– HPV types not covered by the vaccine

– HPV types to which a person has previously been exposed through sexual activity

Not all vulvar, vaginal, and anal cancers are caused by HPV, and GARDASIL protects only against those vulvar, vaginal, and anal cancers caused by HPV Types 6, 11, 16 and 18.

GARDASIL is not a treatment for external genital lesions; cervical, vulvar, vaginal, anal, oropharyngeal and other head and neck cancers; or cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VaIN), or anal intraepithelial neoplasia (AIN).

Vaccination with GARDASIL may not result in protection in all vaccine recipients.

Select Safety Information for GARDASIL

GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL.

Because vaccinees may develop syncope, sometimes resulting in falling with injury, observation for 15 minutes after administration is recommended. Syncope, sometimes associated with tonic-clonic movements and other seizure-like activity, has been reported following HPV vaccination. When syncope is associated with tonic-clonic movements, the activity is usually transient and typically responds to restoring cerebral perfusion. Safety and effectiveness of GARDASIL have not been established in pregnant women. The most common (≥1.0%) adverse reactions were headache, fever, nausea, dizziness; and injection-site pain, swelling, erythema, pruritus, and bruising. The duration of immunity of GARDASIL has not been established.

Dosage and Administration

GARDASIL should be administered intramuscularly in the deltoid or anterolateral area of the thigh.

For GARDASIL, a complete vaccination regimen for individuals 9 through 26 years of age consists of 3 doses at the following schedule: 0, 2 months, 6 months.

On January 8, 2025 Annals of Oncology (IF: 56.7), a top oncology journal globally, reported remarkable long-term follow-up results of a phase 1b/2 clinical trial on Disitamab Vedotin (DV) (developed by Remegen Co., Ltd) combined with Toripalimab in treating locally advanced or metastatic urothelial carcinoma (la/mUC) (NCT04264936, study ID: RC48-C014) (Press release, RemeGen, JAN 8, 2025, View Source [SID1234649522]). This trial was supervised by Professor Jun Guo and Professor Xi’nan Sheng’s teams from Peking University Cancer Hospital.

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It is the first time that long-term follow-up data has been released for a HER2-targeted antibody-drug conjugate (ADC) and PD-1 inhibitor combination therapy in treating la/mUC, marking it a significant milestone. The nearly-three-year follow-up data revealed an objective response rate (ORR) of 73.2% and median overall survival (OS) of 33.1 months, superior to data published from any other prospective clinical studies on ADC plus PD-1 combination therapies for la/mUC.

New Treatment Options for Patients with La/mUC

UC is the sixth most common cancer worldwide. GLOBOCAN 2022 estimated the year 2021 saw 614,298 new cases and 220,596 deaths of UC. In recent years, the prognosis for patients with la/mUC has significantly improved with new drugs and combination therapies approved, among which ADCs demonstrated outstanding potential.

As a HER2-targeted ADC, DV has been approved in China for patients with HER2-overexpressing (defined as immunohistochemistry [IHC] test results of 2+ or 3+) la/mUC previously treated with platinum-containing chemotherapy. The approval is based on the pooled results of two studies (NCT03507166 and NCT03809013, study IDs: RC48-C005 and RC48-C009) where the ORR registered 50.5% and the median duration of response (DOR) registered 7.3 months.

Multiple clinical studies on la/mUCin recent years have confirmed the synergistic antitumor effects of ADC combined with immunotherapy. NCT04264936 offered stronger evidence as its long-term follow-up results published in the Annals of Oncology demonstrated the high response rate, significant survival benefits, and manageable safety profile of the DV and Toripalimab combination therapy.

DV Combined with Toripalimab: High Response Rate and Prolonged Survival

NCT04264936 is an open-label, multicenter, investigator-initiated phase 1b/2 clinical trial investigating the safety and efficacy of DV in combination with Toripalimab for the treatment of patients with HER2-expressing la/mUC. The dose-escalation study (phase 1b) assessed two dose levels of DV (1.5 and 2.0 mg/kg) combined with Toripalimab (3.0 mg/kg) to determine the recommended phase 2 dose which was then evaluated in the dose-expansion stage (phase 2).

From August 2020 to December 2021, 41 patients were enrolled with a median age of 66 years. 53.7% of the participants were male, 70.7% had an ECOG performance status score of 1, 17 (41.5%) had lung metastasis, and 10 (24.4%) had liver metastasis.

As of March 1, 2024, among all participants, the ORR was 73.2% with 4 (9.8%) achieving complete response and 26 (63.4%) achieving partial response, the DCR was 90.2%, the median progression-free survival (PFS) was 9.3 months, the median DOR was 8.6 months, the median OS was 33.1 months and the 36-month OS rate was 49.2%.

Subgroup analysis revealed ORR benefits across all subgroups regardless of the number of prior lines of systemic treatments, HER2 expression (IHC 1+/2+/3+), and PD-L1 expression status. The ORRs for chemotherapy-naïve patients and those who progressed on platinum-based chemotherapy were 76.0% (19/25) and 68.8% (11/16), respectively. The ORRs for patients with HER2 IHC 3+, 2+, 1+, or 0 were 80.0%, 84.2%, 64.3%, and 33.3%, respectively. Compared with the three HER2 IHC 0 participants (one of whom achieved partial response), those with HER2 expression (IHC 1+/2+/3+) had a higher ORR (76.3% vs 33.3%) and longer PFS (median PFS: 9.3 vs 1.7 months).

In summary, the DV and Toripalimab combination therapy has preliminarily demonstrated promising efficacy and manageable safety profile among patients with la/mUC, wherein those with HER2 expression (IHC 1+/2+/3+) achieved high response rates and long-term survival benefits. These findings support the further exploration and validation of the benefits of DV combined with PD-1 inhibitors in treating la/mUC.

On January 8, 2025 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a late-stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported a business outlook and outlined expected upcoming milestones (Press release, Moleculin, JAN 8, 2025, View Source [SID1234649507]).

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"We have positioned Moleculin to achieve value-driving milestones through the next several years, starting with the imminent beginning of enrollment for MIRACLE and the first interim read-out from that study later this year. Having a readout in the first year of a Phase 3 approval trial is, we believe, exceptional. Prior data support our belief that Annamycin is a potential game-changing asset for the treatment of AML, and we believe it can lead to significant value creation for Moleculin as we aggressively move forward with our clinical development plan. Not only has Annamycin appeared to be safer and more effective than currently prescribed anthracyclines, but we believe the recently announced preclinical data demonstrating significant activity of Annamycin in a Venetoclax-resistant AML model underscores the potential that Annamycin has ‘pipeline in a product’ potential and represents a much-needed treatment option for other patients who otherwise have very poor outcomes. Annamycin’s performance in Phase 2 has outperformed the response rates seen in billion-dollar assets in the AML space and AML remains among the highest unmet needs in healthcare. Simply stated, the bar for approval is low, and the potential reward for shareholders is substantial and we have never been more excited about the prospects for Annamycin," commented Walter Klemp, Chairman and CEO of Moleculin.

Clinical Development Update

Relapsed or Refractory Acute Myeloid Leukemia (AML)

The Company is currently advancing the development of Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as "AnnAraC") to a Phase 3 pivotal trial for the treatment of AML patients who are refractory to or relapsed after induction therapy (R/R AML). This Phase 3 "MIRACLE" trial (derived from Moleculin R/R AML AnnAraC Clinical Evaluation) will be global, including sites in the US, Europe and the Middle East.

The MIRACLE study, subject to appropriate future filings with and potential additional feedback from the FDA and their foreign equivalents, utilizes an adaptive design whereby the first 75 to 90 subjects will be randomized (1:1:1) in Part A of the trial to receive high dose cytarabine (HiDAC) combined with either placebo, 190 mg/m2 of Annamycin, or 230 mg/m2 of Annamycin, which Annamycin doses were specifically recommended by the FDA in the Company’s end of Phase 1B/2 meeting. The amended protocol allows for the unblinding of preliminary primary efficacy data (CR) and safety/tolerability of the three arms at 45 subjects, in addition to the conclusion of Part A (at 75 to 90 subjects). This early unblinding will yield 30 subjects with Annamycin (190mg/m2 and 230/m2) and HiDAC and 15 subjects with just HiDAC. The Company expects to reach the first unblinding (45 subjects) in the second half of 2025, in addition to the second unblinding, which is expected in the first half of 2026. This accelerated estimated timeline is due to the positive response the Company received in meetings during December with potential investigators regarding recruitment for the trial.

For Part B of the trial, approximately 244 additional subjects will be randomized to receive either HiDAC plus placebo or HiDAC plus the optimum dose of Annamycin (randomized 1:1). The selection of the optimum dose will be based on the overall balance of safety, pharmacokinetics and efficacy, consistent with the FDA’s new Project Optimus initiative. This increase from 240 to 244 subjects represents the statistical "cost" of the additional interim unblinding.

Important Development Program Highlights

Phase 3 MIRACLE trial builds off of positive results of Phase 1B/2 clinical trial evaluating AnnAraC for the treatment of subjects with AML as both first line therapy and for subjects who are refractory to or relapsed after induction therapy (MB-106):
Complete Remission (CR) rate was 50% and CRc (CR plus CRi (CR with incomplete recovery of blood counts)) rate was 60% for 2nd line subjects (n=10);
Median durability: ~8 months and increasing;
Median overall survival in MB-106 was 9.1 months for 0-6 prior lines of therapies (n=22) and 11.6 months for 2nd line subjects (n=10); and
Strong efficacy signal even where a prior venetoclax combination therapy has failed.
Received US Institutional Review Board (IRB) approval;
Leveraging expertise of Catalyst Clinical Research, a leading contract research organization (CRO), with our recent engagement with them to help conduct the MIRACLE trial; and
Accelerated planned unblinded data readout to H2 2025.
Expected Milestones for Annamycin AML Development Program

1Q – 3Q 2025 – Update on MIRACLE trial site selection/approvals by countries
1Q 2025 – First subject enrolled and treated in MIRACLE trial
2025 – Recruitment update for MIRACLE trial
2H 2025 – Data readout (n=45) unblinded efficacy/safety review
2H 2025 – 2026 – Impact of data readout (n=45) on regulatory pathway; Recruitment update
1H 2026 – Interim efficacy and safety data (n=~75-90) unblinded and Optimum Dose set for MIRACLE trial
2027 – Begin enrollment of 3rd line subjects in MIRACLE2
2027 – Enrollment ends in 2nd line subjects
2028 – Primary efficacy data for 2nd line subjects in MIRACLE
2028 – Begin submission of a Rolling New Drug Application (NDA) for the treatment of R/R AML for accelerated approval on primary endpoint of CR from MIRACLE
Soft Tissue Sarcoma (STS) Lung Metastases

As previously announced, the Company completed enrollment in the Phase 2 portion of its U.S. Phase 1B/2 clinical trial evaluating Annamycin as monotherapy for the treatment of soft tissue sarcoma lung metastases. Subjects who had stable disease at the time of study discontinuation were followed for progression free response and overall survival. The study database is locked, and the clinical study report is being written and should be completed in early 2025 and will be released in detail at that time.

Expected Milestones for Annamycin STS Lung Mets Development Program

2025 – Final MB-107 data readout
2025 – Identify next phase of development / pivotal IIT (investigator-initiated-trial) program
Annamycin currently has Fast Track Status and Orphan Drug Designation from the FDA for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA).

On January 8, 2025 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported corporate updates and highlighted upcoming milestones for 2025 (Press release, Adicet Bio, JAN 8, 2025, View Source [SID1234649523]).

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"2024 was a momentous year for Adicet as we amplified our efforts in autoimmune diseases and solid tumors. We dosed our first patients in our clinical trials evaluating our gamma delta 1 chimeric antigen receptor (CAR) T cell candidates, ADI-001 in LN and ADI-270 in ccRCC. Notably, ADI-270 is the first gamma delta CAR T cell therapy to enter clinical development for solid tumors, underscoring our commitment to pioneering innovative treatments. In the first half of 2025, we look forward to reporting preliminary data for both programs," said Chen Schor, President and Chief Executive Officer at Adicet Bio. "Within our autoimmune portfolio, the successful expansion of our Phase 1 trial of ADI-001 into six autoimmune indications, building upon clinical biomarker data demonstrating ADI-001’s robust tissue trafficking and complete CD19+ B cell depletion in secondary lymphoid tissue, further reinforces ADI-001’s potential as an off-the-shelf treatment option.

Mr. Schor continued: "In our oncology pipeline, the initiation of our Phase 1 trial of ADI-270 in ccRCC patients marked a crucial achievement as the first gamma delta 1 CAR T cell product candidate for the treatment of solid tumors. As we look ahead to 2025, we believe we are well positioned to build on this momentum to advance our product candidates to patients living with autoimmune diseases and cancer."

Clinical Program Progress and Upcoming Milestones:

Autoimmune Diseases Clinical Programs

In June 2024, the Company announced that the Food and Drug Administration (FDA) had granted Fast Track Designation to ADI-001 for the potential treatment of relapsed/refractory class III or class IV LN.
In September 2024, Adicet presented clinical biomarker data from the Phase 1 GLEAN trial of ADI-001 at the 9th Annual CAR-TCR Summit demonstrating robust tissue trafficking resulting in high levels of ADI-001, significant CAR T cell activation, and complete CD19+ B cell depletion in secondary lymphoid tissue.
In October 2024, the Company received FDA clearance for an amendment to its Investigational New Drug (IND) application to evaluate ADI-001 in IIM and SPS as part of the Phase 1 trial of ADI-001 in autoimmune diseases. This followed the clearance of an IND amendment in August 2024 to expand clinical development of ADI-001 in the Phase 1 trial beyond LN to include SLE, SSc and AAV.
In November 2024, Adicet announced the dosing of the first LN patient in the Phase 1 trial of ADI-001 in autoimmune diseases. The Company expects to initiate enrollment for patients with SLE, SSc, IIM, and SPS in the first quarter of 2025, and for patients with AAV in the second half of 2025.
Preliminary clinical data from the Phase 1 trial of ADI-001’s LN patient cohort are anticipated in the first half of 2025. Preliminary data from the Phase 1 trial’s other patient cohorts are expected in the second half of 2025.
Hematologic Malignancies and Solid Tumor Clinical Programs

In April 2024, Adicet presented preclinical data for ADI-270 at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) showing robust anti-tumor activity in an in vivo model of ccRCC, including tumor infiltration, resistance to the immunosuppressive tumor microenvironment, and potent activity via CAR and innate-mediated targeting.
In July 2024, the Company announced that FDA Fast Track Designation had been granted to ADI-270 for the potential treatment of patients with metastatic/advanced ccRCC who have been treated with an immune checkpoint inhibitor and a vascular endothelial growth factor inhibitor.
In December 2024, Adicet announced the dosing of the first patient in the Phase 1 clinical trial evaluating ADI-270 in patients with metastatic/advanced ccRCC.
Preliminary clinical data from the ADI-270 Phase 1 trial in ccRCC are expected in the first half of 2025.

On January 8, 2025 Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage company developing transformative therapies for the treatment of cancer and rare diseases, reported that management will present at the 43rd Annual J.P. Morgan Healthcare Conference on Thursday, January 16, 2025, at 7:30 am PT in San Francisco (Press release, Protara Therapeutics, JAN 8, 2025, View Source [SID1234649508]).

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A live webcast of the presentation can be accessed by visiting the Events and Presentations section of the Company’s website: View Source The webcast will be archived for a limited time following the presentation.