On January 24, 2024 Genome & Company (KOSDAQ: 314130), a clinical stage biotech leading in microbiome therapeutic development reported on January 18th (local time) that a poster was presented on the positive topline results from the phase 2 clinical trial (NCT05419362) in gastric cancer of its microbiome immunotherapy, GEN-001 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI 2024) (Press release, Genome & Company, JAN 24, 2024, View Source;company-announces-positive-topline-results-from-phase-2-clinical-trial-of-combination-of-gen-001-and-bavencio-for-the-treatment-of-gastric-cancer-poster-presented-at-asco-gi-302042094.html [SID1234639456]).

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GEN-001 is an oral therapeutic candidate consisting of a single strain of Lactococcus lactis, and the phase 2 clinical trial for gastric cancer was conducted in combination with avelumab (Bavencio) developed and commercialized by Merck KGaA, Darmstadt, Germany.

The clinical trial is being conducted at 6 domestic institutions in South Korea on 42 patients with PD-L1-positive advanced gastric cancer or gastroesophageal junction adenoma cancer who has failed second-line or later standard of care treatment regardless of prior immunotherapy. The positive headline results of the interim analysis of the Phase 2 clinical trial were made public in May of last year, and detailed topline results of the Phase 2 clinical trial conducted to date were disclosed for the first time at this ASCO (Free ASCO Whitepaper) GI 2024.

As a result of the efficacy evaluation of 42 patients participating in the phase 2 clinical trial, partial responses (PRs) were observed in 7 out of 42 patients. Furthermore, 3 out of 8 patients among 42 patients who were previously treated by immunotherapy experienced PRs (overall response rate, ORR 37.5%).

In addition, the topline results revealed the median progression free survival (PFS) at 1.7 months and the median overall survival (OS) at 7.9 months.

Under the current frontline immunotherapy landscape in gastric cancer, GEN-001 and Bavencio combination may become an attractive therapeutic option in the salvage setting of gastric cancer. Treatment-related adverse events (TRAEs) were observed in 14 patients out of 42 patients, and only 2 patients experienced grade 3 TRAEs including anemia, fatigue, and pneumonitis. Overall, this combination showed manageable safety and tolerability.

Prof. Jeeyun Lee (M.D.) from the Department of Hemato Oncology at Samsung Medical Center, the coordinating investigator of the study stated, "while there are limited treatment options available for patients with metastatic gastric cancer, combination of GEN-001 and avelumab demonstrated favorable therapeutic effects leading to an extended survival. The overall response rate (ORR) of 37.5% is particularly promising among PD-L1-positive refractory patients to prior immunotherapy. We intend to further validate these results in subsequent clinical studies to establish this treatment regimen as a viable third-line treatment." Expressing enthusiasm, she added, "we are excited that this marks the first clinical study to showcase the potential of microbiome therapeutics in the treatment of gastric cancer."

Dr. Jisoo Pae, CEO of Genome & Company, said, "we are incredibly pleased by our presentation at ASCO (Free ASCO Whitepaper) GI 2024 on the topline data of the phase 2 clinical trial for gastric cancer with our microbiome immuno-oncology treatment, GEN-001. Based on the results, we can confirm not only the results of exceeding the primary endpoints, but also compelling clinical benefits compared to the previously published Bavencio monotherapy data". He continued, "we plan to establish a future development strategy from obtaining further data in response duration, biomarker analysis, and overall survival."

Meanwhile, in addition to the ongoing clinical trials in combination with Bavencio, GEN-001 is currently in another phase 2 combination clinical trial for biliary tract cancer with pembrolizumab (Keytruda), a cancer immunotherapy drug from MSD (a tradename of Merck & Co., Inc., Kenilworth, N.J., USA). Through combination therapy clinical trials with anti-PD-1 and PD-L1 immunotherapy drugs, Genome & Company aims to develop treatments in overcoming the resistance to immunotherapy.

On January 24, 2024 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of conditionally activated, localized biologics, reported that it has received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) applications for the conditionally activated Probody therapeutics CX-2051, an EpCAM-directed ADC, and CX-801, a dually-masked version of interferon-alpha 2b (Press release, CytomX Therapeutics, JAN 24, 2024, View Source [SID1234639455]). CX-2051 has been cleared for the initiation of Phase 1 dose escalation in solid tumors with known EpCAM expression and CX-801 has been cleared for the initiation of Phase 1 dose escalation in solid tumors including melanoma, renal, and head and neck squamous cell carcinoma. Both programs are expected to start Phase 1 studies in the first half of 2024.

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"CX-2051 and CX-801 have the potential to address major unmet needs in oncology and we are excited to advance these programs into Phase 1 clinical studies. CX-2051 is an ADC conjugated to a next-generation topoisomerase-1 inhibitor payload that we believe is tailored to certain EpCAM-expressing tumors, including colorectal cancer," said Wayne Chu, M.D., chief medical officer of CytomX Therapeutics. "CX-801 is designed to overcome previous limitations of interferon-directed therapies due to systemic toxicity and establish CX-801 as a cornerstone of combination regimens, including with checkpoint inhibitors, across a wide range of tumor types," continued Dr. Chu.

"The parallel advancement of these programs toward the clinic demonstrates the continued high productivity of the CytomX team and the versatile, multi-modality nature of our Probody platform. The product design principles behind CX-2051 and CX-801 integrate over a decade of continuous innovation and experience at CytomX," said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX Therapeutics. "We look forward to the clinical initiation of these programs as we enter a potentially milestone-rich period for the company in 2024 and 2025."

About CX-2051

EpCAM is a high potential oncology target that has been clinically validated by locally administered, previously approved cancer therapies. However, to date, efforts to generate systemically administered anti-EpCAM therapeutics have not been successful due to toxicities in certain epithelial tissues, notably in the gastrointestinal tract. CX-2051, a conditionally activated ADC, is tailored to optimize the therapeutic index for EpCAM-expressing cancers. The cytotoxic payload utilized in CX-2051 is a derivative of camptothecin, a topoisomerase-1 inhibitor, a class of drug that has shown potent clinical anti-cancer activity in the ADC context for multiple targets. CX-2051 has demonstrated a wide predicted therapeutic index and strong preclinical activity and tolerability in multiple preclinical models, including colorectal cancer. Phase 1 clinical initiation in EpCAM expressing solid tumors is expected in the first half of 2024. Further details on the design and preclinical optimization of CX-2051 can be found here:

Link to 2023 World ADC Conference presentation

About CX-801

Interferon-alpha 2b is an immunotherapeutic cytokine that has demonstrated clinical activity and gained regulatory approval previously in multiple cancer types, including metastatic melanoma, renal cancer and bladder cancer. IFNα2b provides a potentially superior approach to activating anti-tumor immune responses compared to other cytokines. CX-801 is a dually masked, conditionally activated version of IFNα2b that has the potential to become a cornerstone of combination therapy for a wide range of tumor types, including in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. Phase 1 initiation for CX-801 solid tumors including melanoma, renal, and head and neck squamous cell carcinoma anticipated in the first half of 2024. Further details on the design and preclinical optimization of CX-801 can be found here:

Link to 2023 SITC (Free SITC Whitepaper) poster

On January 24, 2024 VerImmune, Inc., a biotechnology company specializing in Virus-inspired Particle modalities for cancer treatment and other disease areas, proudly reported the issuance of its third U.S. Patent from the U.S. Patent and Trademark Office (USPTO) (Press release, VerImmune, JAN 24, 2024, View Source [SID1234639454]).

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The newly issued patent, U.S. Patent No. 11,858,964 B2, appropriately titled "Virus-inspired Compositions and Methods of Redirecting Pre-existing Immune Responses for the Treatment of Cancer," provides a comprehensive layer of protection and support for VerImmune’s ViP proprietary technology platform. This patent includes a novel ViP composition of matter, along with innovative methods for manufacturing and utilizing the technology in cancer treatment. This patent will safeguard the technology platform until at least 2041, which offers an extensive period of exclusivity and protection.

Additionally, VerImmune is also pleased to also announce that the USPTO has issued a notice of allowance for a continuation patent building upon the success of its previously issued patent, U.S. Patent No. 11,285,203, entitled "Chimeric virus-like particles and uses thereof as antigen-specific redirectors of immune responses," This new additional patent will provide additional claim scope, broadening the protection of VerImmune’s first issued patent family.

Collectively, these latest developments further solidify VerImmune’s intellectual property moat at the forefront of cutting-edge cancer treatment technologies.

VerImmune’s revolutionary platform is currently focused on redirecting the body’s pre-existing T-cell memory against pathogens, effectively harnessing its power to combat cancer. With the potential to target multiple types of cancer, the technology’s versatility arises from the near-universal nature of pre-existing responses triggered by childhood vaccines and past infections. As a result, VerImmune’s patented technology holds promise for broad applications in cancer treatment, marking a significant stride towards more effective and inclusive solutions.

On January 24, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported the submission of the Chemistry, Manufacturing, and Controls (CMC) section of the New Drug Application (NDA) for UGN-102 (mitomycin) for intravesical solution to the U.S. Food and Drug Administration (FDA) (Press release, UroGen Pharma, JAN 24, 2024, View Source [SID1234639452]).

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"The submission of the CMC portion of the NDA for UGN-102 marks a significant milestone for UroGen and underscores our dedication to advancing innovative therapies for the benefit of individuals grappling with low-grade, intermediate-risk non-muscle invasive bladder cancer," said Liz Barrett, President and CEO, UroGen. "We look forward to working closely with the FDA throughout the review process and remain steadfast in our commitment to address unmet medical needs in the uro-oncology space and advance patient care."

The objective of the rolling NDA for UGN-102 is to facilitate early engagement with the FDA, and a more efficient and timely review of the NDA. Based on its agreement with the FDA, UroGen will complete the submission of the rolling NDA for UGN-102 in 2024 with a potential FDA decision as early as the first quarter of 2025.

The CMC section of a regulatory submission typically includes information about the drug product such as its physicochemical properties, formulation, methods of manufacture, specifications, stability data, and analytical methods used to test the product.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of low-grade, intermediate-risk, non-muscle invasive bladder cancer (LG-IR-NMIBC). Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates completing its NDA submission for UGN-102 in 2024 with a potential FDA decision as early as the first quarter of 2025.

On January 24, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported 2023 year-end Annamycin clinical trials preliminary data and 2024 expectations for multiple data readouts and a transition to pivotal Phase 2B/3 clinical studies (Press release, Moleculin, JAN 24, 2024, View Source [SID1234639451]). The Company also updated its upcoming milestones.

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"Over the course of 2023, we delivered on our promise for a year of important data from our Annamycin clinical development programs. We are well-positioned to continue building upon our encouraging growing body of preliminary clinical data and transition to pivotal Phase 2B/3 clinical trials by year-end 2024. We believe that Annamycin should be positioned as a 2nd line therapy for acute myeloid leukemia or AML, and for the first time ever, should enable a clear majority of patients to benefit from anthracyclines. Anthracyclines continue to represent one of the most important treatments for AML and advanced soft tissue sarcoma," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin.

Mr. Klemp continued, "Our progress is accelerating. Last month, we reported strong results from our first 11 patients in our AML clinical trial. Now, just weeks later our evaluable patients have increased to 15 and the results are even stronger. Enrollment continues to be robust, and we expect to announce the completion of enrollment of 2nd line patients by the time we announce financial results at the end of March, if not sooner. We believe that data will present a clear picture of the approvability of Annamycin and will support our discussions with the FDA for developing an accelerated approval pathway as a 2nd line therapy for relapsed and refractory AML, including a pivotal approval clinical trial we expect to begin before the end of 2024. With our recent financing in December 2023, we have extended our runway into the fourth quarter of 2024, as well. We thank our investors and collaborators for their support in 2023 and we look forward to an exciting and prosperous 2024."

Preliminary 2023 Year-End Annamycin Clinical Trials Data

AML

The Company is currently conducting its Phase 1B/2 clinical trial evaluating 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) 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). clinicaltrialsregister.eu: EudraCT 2020-005493-10 or clinicaltrials.gov: NCT05319587. The Company has also begun recruiting 1st line subjects into this trial. The Company continues to treat subjects in the Phase 2 portion of the study. Below is a summary of the data to date on this trial which is preliminary and subject to change.

Among subjects who had an evaluable post treatment bone marrow biopsy, or who dropped out due to an adverse event (AE), there have been 6 complete responses (CR’s) and 1 complete response with incomplete recovery of platelets and/or neutrophils or 40% CR and 47% CR/CRi’s of the intent to treat (ITT) subjects (N=15) and 46% CR’s and 54% CR/CRi’s of the subjects treated (dosed with Annamycin) (N=13). Two subjects experienced adverse events and were not dosed per protocol with one having an allergic reaction to Annamycin, the first the Company has seen in over 70 subjects dosed in the Company’s multiple Annamycin clinical trials; the second adverse event was due to an allergic reaction to cytarabine. The CR/CRi’s have been spread across 3 different sites in two different countries (Poland and Italy) and 7 out of 9 sites participating in the study have recruited subjects to date.
The Company has expanded the study protocol to include a cohort of 1st line subject which should provide data to enable the designing of a potential confirmatory Phase 3 post-approval study, however it does not expect the addition of this cohort to delay its End of Phase 2 (EOP2) Meeting with the FDA, which will focus primarily on securing an accelerated approval pathway for the treatment of 2nd line patients (those who were relapsed from or refractory to a 1st line AML therapy). The first 1st line therapy AML subject for Annamycin was recruited, treated, and upon evaluation it was determined that the treatment resulted in a CR.
The first CR subject was treated in February of 2023. The Company has not been notified of any relapses to date, indicating significant durability of the CRs being generated in this study.
There continues to be no evidence of cardiotoxicity as reported by an independent expert’s reports following assessments of ejection fractions, strain analyses, ECGs, and cardiac biomarkers including Troponin-I and T cross all trials (N=62). Most subjects have experienced myelosuppression, febrile neutropenia and/or thrombocytopenia, which are common adverse events with other anthracyclines.

Currently, the median age of the 15 intent to treat subjects in MB-106 is 69 years (range of age is 32 to 78 years) with a median number of prior therapies for AML of 1 (range of 0 to 6).
The Company has recruited 19 subjects to date with 2 subjects withdrawing from the trial due to adverse events and 4 other subjects not yet having a bone marrow aspirate fully evaluable. The Company may recruit up to 28 subjects in the Phase 1B/2 clinical trial. At the Company’s current rate of recruitment for the study, Moleculin expects to complete recruitment and report topline data in 1H 2024, if not by the end of the first quarter.
STS Lung Mets

On September 21, 2023, Moleculin announced the completion of 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 (MB-107) clinicaltrials.gov: NCT04887298. All subjects had pulmonary metastasis from soft tissue sarcoma (STS Lung Mets or STS) and at least one prior therapy. There was no limit on how many prior therapies a subject could have prior to entering this study. Most subjects were heavily treated with other therapies prior to entering our trial with our treatment representing the 4th median therapy for all subjects in the Phase 1B and Phase 2 portion of the trial (range of 2 to 12). Below is a summary of the data to date on this trial which is preliminary and subject to change.

The Company previously announced the preliminary data from the Phase 1B portion of the study showing median progression free survival (PFS) for 67% of the Phase 1B subjects of over 2 months (N=15) and median overall survival (OS) of 11.3 months. Not including the one subject that withdrew from OS follow-up the median OS increased to 13 months.
Additionally, the Company noted that Phase 1B subjects with less than or equal to 2 prior treatments and treated at the recommended Phase 2 dose or lower demonstrated a higher percentage of subjects with PFS of 2 months or greater at 78% (N=9).
Of the 17 subjects in the Phase 2 portion of the study, all treatments have ceased, and subjects are being followed for PFS and OS. A majority of subjects remain alive at this time. The Company believes that the data will be similar to or better than the Phase 1B portion of the study and will announce the results once the study has substantively concluded.
2024 Expected Upcoming Milestones

The Company announces the updated expected upcoming milestones for 2024.

Annamycin

AML
1H 2024: In-depth data review and presentation of topline data on MB-106 clinical trial.
1H 2024: MB-106 End of Phase 2 (EOP2) Meeting with the FDA and/or its European equivalent.
Mid 2024: Identify next phase of development/pivotal program.
Late 2024 into 1H 2025: Initiate pivotal program.
STS Lung Mets
2H 2024: Final MB-107 data readout.
2024: Identify next phase of development/pivotal program.
Late 2024 into 1H 2025: Initiate 1st line STS study with an investigator-initiated trial.
Other Drug Candidates

Moleculin is in ongoing discussions with multiple academic institutions in separate programs evaluating WP1066 for the treatment of glioblastomas and/or pediatric brain tumors. The Company expects to finalize agreements with Northwestern University for an investigator-initiated and funded trial in early 2024 (clinicaltrials.gov: NCT05879250).

Expected Upcoming Milestones

Report topline results from investigator-initiated Phase 1 study in pediatric brain tumors.
Announce results of formulation efforts for intravenous delivery.
Expect the commencement of an externally funded investigator-initiated adult clinical trial to be announced in 1H 2024. Seeking investigator-initiated pediatric cancer clinical trial in 2H 2024.
WP1122 was developed as a prodrug of 2 deoxy-D-Glucose (2-DG) to provide a more favorable pharmacological profile and was found to have greater potency than 2-DG monotherapy in preclinical models where tumor cells require higher glycolytic activity than normal cells. WP1122 has also been shown to have a greater antiviral effect than 2-DG against SARS-CoV-2 in MRC-5 cells in culture. The improved pharmacokinetic and pharmacodynamic (PK/PD) profile of WP1122 compared to 2-DG was noted in mice following oral dosing at equimolar (i.e., equivalent levels of 2-DG) doses. WP1122 successfully completed a Phase 1 clinical trial, which established a recommended safe dose for future potential Phase 1B or Phase 2 clinical trials. The WP1122 Portfolio includes numerous analogs, including WP1096, which has demonstrated the potential for broad antiviral capabilities in a wide range of in vitro models including multiple arenaviruses, filoviruses, Zika virus, and HIV. The Company looks forward to the potential for additional externally funded research to confirm such activity.

Expected Upcoming Milestones

Report preliminary findings of National Institutes of Health (NIH) funded animal testing of WP1096 in the Tacaribe Arenavirus.
Identify investigators interested in initiating a clinical trial to study the safety, pharmacokinetics, and efficacy of oral WP1122 in adult patients with GBM.