On May 26, 2023 Shuttle Pharmaceuticals Holdings, Inc. (Nasdaq: SHPH), a discovery and development stage specialty pharmaceutical company focused on improving outcomes for cancer patients treated with radiation therapy (RT), reported a corporate update in connection with the filing of its Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 (Press release, Shuttle Pharmaceuticals, MAY 26, 2023, View Source [SID1234632154]).

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Recent Highlights

Shuttle Pharma continues to execute on the necessary steps to advance Ropidoxuridine, the Company’s lead clinical sensitizer drug candidate, towards the commencement of its upcoming Phase II clinical trial in brain cancer patients undergoing radiation therapy with an expectation of pre-IND application submission to the FDA by the end of the second quarter of 2023.
Entered into agreements with TCG GreenChem, Inc. and UI Pharmaceuticals for drug manufacture and formulation development of Ropidoxuridine, the Company’s lead clinical sensitizer drug candidate, for use in the Company’s upcoming Phase II clinical trial evaluating Ropidoxuridine in combination with radiation therapy for the treatment of glioblastoma.
Engaged Theradex Oncology, a leading clinical research organization, to help prepare for its upcoming clinical study of Ropidoxuridine.
Entered into an agreement to lease new laboratory and office space, commencing in June 2023, to assist in furthering the development of the Company’s lead drug candidates and accelerate broader diagnostic capabilities on predictive biomarkers.
Entered a research agreement with Georgetown University focused on the evaluation of the Company’s lead HDAC6 inhibitor candidate, SP-2-225, evaluating the anti-tumor effect of the combination of SP-2-225 and RT in a syngeneic breast cancer model.
Shuttle Pharma was awarded U.S. Patent No. 11,654,157, "Methods And Compositions For Cancer Therapies That Include Delivery Of Halogenated Thymidines And Thymidine Phosphorylase Inhibitors In Combination With Radiation," which was issued by the U.S. Patent and Trademark Office on May 23, 2023.
Published manuscripts discussing prostate cancer cell lines derived from African American men for precision medicine and immune responses taking place in patients after radiation therapy for cancer.
Awarded patents in the U.S. and Hong Kong for its radiation sensitizing HDAC inhibitor technology platform.
Appointed Dr. Bette Jacobs to its Board of Directors as an independent director.
Rang the Nasdaq opening bell in January 2023.
Closed on private placement of $4.3 Million of Senior Secured Convertible Note and Warrants to purchase 1.018 million shares of common stock in exchange for $4.0 million investment.
At March 31, 2023, the Company had a working capital balance of $9 million. The Company anticipates that it has sufficient capital to fund operations into the first quarter of 2025.
"Shuttle Pharma is advancing our mission to improve the lives of cancer patients by developing therapies that are designed to maximize the effectiveness of Radiation Therapy while limiting the late effects of radiation in cancer treatment," commented Shuttle Pharma’s Chairman and CEO, Anatoly Dritschilo, M.D. "During the first quarter, we made tangible progress advancing our pipeline, including Ropidoxuridine, our lead clinical drug candidate, which sensitizes rapidly growing cancer cells and, our various selective HDAC (histone deacetylase) inhibitors – which sensitize cancer cells and stimulate the immune system. With Ropidoxuridine, we are finalizing details to submit the final protocol details to the FDA at the end of the second quarter of 2023 with commencement of the Phase II clinical trial in brain cancer patients commencing shortly thereafter. Additionally, we are advancing pre-clinical work to support our IND-enabling studies in 2023 with a goal to submit an investigational new drug application (IND) for the selective HDAC6 inhibitor and initiation of a Phase I clinical trial in 2024. We look forward to an exciting 2023 as we advance our immuno-oncology and radio-oncology solutions."

Radiation Therapy Sensitizer Platform

Radiation therapy is a proven modality for cancer treatment. By developing radiation sensitizers, Shuttle Pharma aims to increase cancer cure rates, prolong patient survival and improve quality of life when radiation is used as a primary treatment, or in combination with, surgery, chemotherapy and immunotherapy.

Modern oncology incorporates multi-modality strategies that use combinations of surgery, chemo or immunotherapy, and radiation to treat cancers. Radiation therapy requires delivery and shaping of high doses of radiation energy to tumors to kill or slow the growth of cancer cells by damaging their cellular DNA. State-of-the-art technologies to deliver the radiation doses include image guided treatments with linear accelerators and particle radiation with protons. However, radiation therapy of adjacent healthy tissues can lead to injuries of normal organs. The addition of radiation sensitizers allows preferential increased killing of cancer cells.

Currently, there is only one drug on the market approved by the FDA as a radiation sensitizer. However, that drug has a host of side effects that limit its utility. Other drugs are used "off label" by radiation oncologists, but these often have additional side effects. There is an urgent need for an effective radiation sensitizer with low toxicity for use in combination with radiation therapy.

Shuttle Pharma’s lead candidate, Ropidoxuridine, is an orally available prodrug, that once ingested, metabolizes into iododeoxyuridine, a pyrimidine analog, that has been recognized as a radio sensitizing agent since the 1960s. The Company is advancing its planned Phase II clinical trial of Ropidoxuridine in brain cancer patients undergoing radiation therapy for glioblastoma. Shuttle is currently preparing the Investigational New Drug application for the study with an expectation of final submission to the FDA at the end of the second quarter of 2023.

Beyond Ropidoxuridine, Shuttle is also developing a platform of HDAC inhibitors (SP-1-161, SP-2-225 and SP-1-303), with SP-2-225 being Shuttle Pharma’s lead HDAC inhibitor for preclinical development. SP-2-225 has effects on the regulation of the immune system. The interactions of RT with the immune response to cancers are of great current interest, offering insight into potential mechanisms for primary site and metastatic cancer treatment. Shuttle Pharma is currently advancing drug manufacture and IND-enabling studies to enable a Phase I clinical trial in 2024.

Various sources have estimated that more than 900,000 patients are treated annually in the U.S. with radiation therapy for their cancers. About 50% are treated for curative purposes and the balance for palliative care. The market opportunity for radiation sensitizers lies with the 450,000 patients treated with curative intent. Based on a rough estimate of a course of radiation sensitizing brand drug therapy, which are used off label at this time, the potential market size is estimated to be in excess of $4.5 billion annually.

On May 26, 2023 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies ("ETBs"), to create novel therapies with potent differentiated mechanisms of action for cancer, reported the presentation of a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting, taking place June 2-6, 2023 in Chicago, IL (Press release, Molecular Templates, MAY 26, 2023, View Source [SID1234632153]). One-on-one meetings may be scheduled directly with Molecular Templates.

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The poster will highlight interim efficacy and safety data on MT-6402, MTEM’s ETB program designed to activate T-cells through direct cell-kill of immunosuppressive PD-L1+ immune cells. MT-6402 can also deliver and induce the presentation of an MHC class I CMV antigen on tumor cells (antigen seeding mechanism of action) for pre-existing CD8 T-cell recognition and destruction in HLA-A*02/CMV+ patients with high PD-L1 expression on their tumors. MT-6402 continues to demonstrate pharmacodynamic effects and monotherapy activity in heavily pre-treated checkpoint therapy experienced patients. To date, no instances of capillary leak syndrome or other manifestations of innate immunity have been observed with any next-generation ETB.

Details
Presentation Title: MT-6402, an engineered toxin body (ETB) targeting PD-L1: Interim efficacy and safety data
Poster Number: 2552
Session: Developmental Therapeutics – Immunotherapy
Date/Time: 8 – 11am CST Saturday, June 3, 2023
Location: Board #394, Hall A (McCormick Place)
The poster will be available in the Presentations section of MTEM’s website.

On May 26, 2023 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that a poster presentation featuring the design of its Phase 1 clinical trial, evaluating the Company’s Self-Assembly DisAssembly Pre-targeted Radioimmunotherapy ("SADA Y-PRIT") Theranostic Platform for the treatment of certain GD2-positive solid tumors, including small cell lung cancer, sarcoma and malignant melanoma will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting to be held June 2-6, 2023 in Chicago, Illinois (Press release, Y-mAbs Therapeutics, MAY 26, 2023, View Source [SID1234632152]).

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The Phase 1 dose-escalation, single-arm, open-label, non-randomized, multicenter trial (NCT05130255) has three parts: Part A will explore dose-finding for the GD2-SADA molecule and testing of dosing intervals between the protein and the 177Lu-DOTA payload; Part B will determine the optimal dose of 177Lu-DOTA; and Part C will evaluate safety and initial signals of efficacy using repeated dosing. Dose escalation is based two patients in cohort 1 and 2, followed by a classical 3+3 design. The study is actively enrolling, and the Company expects Parts A, B, and C will include 18, 12, and 32 patients, respectively, across 6-10 U.S. sites.

The GD2-SADA construct was created using the Company’s SADA Y-PRIT Theranostic Platform, which was licensed by the Company from Memorial Sloan Kettering Cancer Center ("MSK") and Massachusetts Institute of Technology ("MIT"). In research, it was shown that SADA Y-PRIT utilizes a pre-targeted payload delivery method where antibody constructs assemble into tetramers and bind to the tumor target. In prior nonclinical studies, unbound constructs predictably disassembled into smaller antibody fragments and were taken up by the liver or excreted through the kidneys within a few days after administration. In a second infusion, a radioactive payload designed specifically to target the SADA molecules attached to the tumor target. Y-mAbs believes this approach provides the possibility of targeting tumors with precision while minimizing radiation of normal tissues, and that the SADA Y-PRIT Theranostic Platform may have the potential to deliver a variety of payloads and be developed against multiple tumor targets, as well as for theranostic purposes.

Researchers at MSK developed the SADA technology for radioimmunotherapy, which is exclusively licensed by MSK to Y-mAbs. MSK has institutional financial interests related to the technology and Y-mAbs.

On May 26, 2023 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company discovering and developing clinically differentiated small molecule therapeutics targeting fundamental biological pathways of cancers, reported positive data from the Phase 1b trial of azenosertib, the Company’s potentially first-in-class WEE1 inhibitor, in combination with chemotherapy in patients with platinum-resistant ovarian cancer (Press release, Zentalis Pharmaceuticals, MAY 26, 2023, View Source [SID1234632151]). Azenosertib was well tolerated in combination with multiple types of chemotherapy and demonstrated encouraging clinical activity, with noteworthy improvements in objective response rates (ORRs) and median progression free survival (mPFS) in all patients, especially those with Cyclin E1+ tumors, a subgroup recognized to have a poor prognosis and be refractory to chemotherapy. Results will be presented in a poster discussion session at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting on June 5th (Abstract #5513).

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"Azenosertib is emerging as a very promising clinical candidate, with demonstrated anti-tumor activity in difficult-to-treat tumor types when used in combination with standard chemotherapy regimens," said Kimberly Blackwell, M.D., Chief Executive Officer of Zentalis. "The addition of azenosertib increased ORRs and mPFS over those observed historically with chemotherapy alone, or compared to adavosertib in combination with chemotherapy. We are very encouraged by our robust chemotherapy combination data, particularly the strong efficacy and tolerability results when dosing azenosertib intermittently. These data provide a compelling rationale to advance azenosertib into a registrational study in combination with either carboplatin or paclitaxel in Cyclin E1+ ovarian cancer. We look forward to providing additional insights into our azenosertib clinical programs and the franchise potential we see for this product candidate during our June 6 investor webcast."

Efficacy and Safety Results:

A total of 115 patients were enrolled in the study across all chemotherapy combination groups. At the data cut-off of April 10, 2023, 94 were efficacy evaluable. Across all dosing schedules, azenosertib plus paclitaxel demonstrated the highest ORR of 50.0% (mPFS of 7.4m), followed by an ORR of 38.5% (mPFS of 8.3m) for azenosertib plus gemcitabine. Azenosertib plus carboplatin demonstrated an ORR of 35.7% (mPFS of 10.4m), and azenosertib plus PLD demonstrated an ORR of 19.4% (mPFS of 6.3m).

A total of 82 response-evaluable patients had available Cyclin E1 expression data by immunohistochemistry (IHC). Cyclin E1+ status (H-score >50) was associated with a superior ORR and a longer mPFS across the total patient population (ORR of 40.0% vs 8.3%; mPFS of 9.86 vs 3.25 months, HR = 0.37; P = 0.0078), showcasing the potential synergy of WEE1 inhibition with chemotherapy in this patient population.

Overall, the tolerability of azenosertib dosed intermittently in combination with either paclitaxel or carboplatin compares favorably to historical data from standard of care chemotherapy doublets of either paclitaxel-carboplatin or PLD-carboplatin. Frequent Grade ≥3 treatment-related adverse events (%) across all azenosertib intermittent dosing groups were thrombocytopenia (27.5%), neutropenia (25.5%), anemia (15.7%), and fatigue (9.8%). A recommended Phase 2 dose was determined for each of the azenosertib combinations with paclitaxel, carboplatin, and PLD.
Based on these results, the Company is planning to initiate a Phase 3 study comparing azenosertib dosed intermittently in combination with either carboplatin or paclitaxel in patients with Cyclin E1+ platinum-sensitive ovarian cancer. The Company expects to initiate the Phase 3 study in the first quarter of 2024.
"The results thus far for azenosertib in combination with chemotherapy are very promising, as there remains high unmet need in this patient population, particularly patients with Cyclin E1+ tumors who historically have not responded well to chemotherapy," said Joyce Liu, M.D., M.P.H., Associate Chief and Director of Clinical Research for the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute. "I look forward to continuing to work with the Zentalis team to advance azenosertib in the clinic and, if approved, ultimately into medical practice as an important and novel treatment option for platinum-sensitive ovarian cancer patients."
Premal H. Thaker, M.D., Professor of Obstetrics and Gynecology, Director of Gynecological Oncology Clinical Research, Division of Gynecologic Oncology, Washington University School of Medicine, and an investigator on the study added, "The data for azenosertib in combination with chemotherapy are increasingly robust and encouraging. Moreover, the enrichment of patients by Cyclin E1+ status provides a compelling strategy for future clinical trials. I look forward to the initiation of a study examining the role of azenosertib in combination with chemotherapy in earlier lines of therapy."

The Company will host a webcast on Tuesday, June 6, 2023 at 8:00 a.m. ET to provide a clinical update, including an overview of the ASCO (Free ASCO Whitepaper) data, as well as safety, pharmacology and efficacy results for azenosertib as a monotherapy, and plans for future development of azenosertib as a monotherapy and in combination with chemotherapy. The corporate webcast will be accessible via the Investors page of Zentalis’ website, www.zentalis.com. The archived webcast and presentation will be available on the Company’s website after the event.

ASCO Presentation Details:
Poster Title: Correlation of Cyclin E1 expression and clinical outcomes in a Phase 1b dose-escalation study of Azenosertib (ZN-c3), a WEE1 inhibitor, in combination with chemotherapy in patients with platinum-resistant or refractory (R/R) epithelial ovarian, peritoneal, or fallopian tube cancer
Presenter: Dr. Liu, M.D., M.P.H., Associate Chief and Director of Clinical Research for the Division of Gynecologic Oncology at the Dana-Farber Cancer Institute.
Session Title: Gynecologic Cancer

Session Date and Time: Monday, June 5, 2023, 1:15 – 4:15 p.m. CT
Location: Hall A
Poster Board Number: 208
Poster Discussion Session Date and Time: Monday, June 5, 2023, 4:30 – 6:00 p.m. CT
Location: S100bc
Abstract Presentation Number: 5513

A video summary of the poster by Dr. Liu will be available on the ASCO (Free ASCO Whitepaper) virtual platform.
Once presented, the poster can be found on the Company’s website using this link.

About Azenosertib
Azenosertib is a potentially first-in-class and best-in-class small molecule WEE1 inhibitor in development for the treatment of cancer. Inhibition of WEE1, a DNA damage response kinase, drives cancer cells into mitosis without being able to repair damaged DNA, resulting in cell death. Currently, there are no FDA-approved WEE1 inhibitors, and azenosertib has been designed for superior selectivity and pharmacokinetic properties. Azenosertib is being developed in therapeutic areas of high unmet need and is being evaluated as a monotherapy, in combination with chemotherapy, and in combination with molecularly targeted agents.

On May 26, 2023 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that a poster presentation featuring interim clinical data on naxitamab, a recombinant, humanized anti-GD2 monoclonal antibody, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF") will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting to be held June 2-6, 2023, in Chicago, Illinois (Press release, Y-mAbs Therapeutics, MAY 26, 2023, View Source [SID1234632150]).

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Patients with high-risk neuroblastoma ("HR-NB") commonly develop metastases in the bone and/or bone marrow. Approximately 15% of HR-NB patients are refractory to induction therapy and approximately 50% will relapse. The ongoing Phase 2 Trial 201 (NCT03363373) evaluates naxitamab in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF") in patients with relapsed or refractory HR-NB with residual disease limited to bone and/or bone marrow. Patients with disease in soft tissues or actively progressing disease were excluded from the trial.

Curie Score ("CS") is a semi-quantitative scoring system used to assess the extent of bone metastases and treatment response. Higher CS indicates more extensive bone involvement and may suggest a poorer prognosis.

An interim analysis of Trial 201 (data cutoff December 31, 2021) included 52 patients in the efficacy group and 74 patients in the safety group. The efficacy analyses included the overall response rate (ORR; complete response or partial response) and the reduction in CS by baseline disease status, i.e., refractory or relapsed disease. Clinically meaningful ORRs and reductions in CS were seen in patients regardless of baseline disease status. The ORR was 58% in patients with refractory disease and 42% in patients with relapsed disease. Furthermore, from a mean baseline CS of 5.5 and 5.7 in the refractory and relapsed subgroups (range 1-20 across the two subgroups), the mean change to end of naxitamab treatment was -4.2 and -1.2, respectively. Maximum reductions in CS for relapsed and refractory subgroups were -17 and -18, respectively. Overall, the most common naxitamab related serious adverse events were hypotension, pain, urticaria, and bronchospasm. Baseline CS did not affect the safety profile of naxitamab. Patients with refractory disease had a lower frequency of serious naxitamab related adverse events compared to patients with relapsed disease.

Naxitamab was licensed by the Company from Memorial Sloan Kettering ("MSK"). MSK has institutional financial interests in the compound.

About DANYELZA (naxitamab-gqgk)

DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication was approved in the United States by the FDA under accelerated approval based on overall response rate and duration of response. Continued approval for this indication is contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest and anaphylaxis, and neurotoxicity, such as severe neuropathic pain and transverse myelitis. See full Prescribing Information (View Source) for complete Boxed Warning and other important safety information.