On May 26, 2023 The Menarini Group ("Menarini"), a leading Italian pharmaceutical and diagnostics company, and Stemline Therapeutics ("Stemline"), a wholly-owned subsidiary of the Menarini Group, reported results from a new analysis of the pivotal EMERALD clinical study that suggest that oral single-agent elacestrant may be effective in ER+, HER2- advanced or metastatic breast cancer patients with Non-Detected ESR1-mut whose disease has progressed within six months of treatment with a CDK4/6i (Press release, Menarini, MAY 26, 2023, View Source [SID1234632156]). Results from this new post-hoc subgroup analysis will be presented at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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!

EMERALD is a Phase 3 registrational trial that demonstrated statistically significant PFS with elacestrant versus SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane). Based on these results, the U.S. Food & Drug Administration (FDA) approved ORSERDU (elacestrant) on January 27, 2023, for the treatment of postmenopausal women or adult men with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

ESR1 mutations are present in up to 40% of ER+, HER2- advanced or metastatic breast cancers, and they are a known driver of resistance to standard endocrine therapy.

Importantly, a previous subgroup analysis of the EMERALD PFS results, which were presented at the San Antonio Breast Cancer Symposium (SABCS) 2022, demonstrated that the duration of prior CDK4/6i treatment was positively associated with longer PFS on elacestrant but not with SOC. For patients with ESR1-mut who were treated with CDK4/6i for ≥12 months prior to randomization on EMERALD, elacestrant achieved a median PFS of 8.6 months versus 1.9 months on SOC, with an absolute difference of 6.7 months, and a 59% reduction in the risk of progression or death (HR=0.41 95% CI: 0.26-0.63).

In this new analysis to be presented at ASCO (Free ASCO Whitepaper) 2023, researchers evaluated treatment with elacestrant in a subgroup of patients with Non-Detected ESR1-mut enrolled in the EMERALD study with rapidly progressing disease. Results for patients whose disease progressed within six months of CDK4/6i therapy demonstrated a median PFS of 5.32 months for the elacestrant arm, compared to 1.87 months for patients who received SOC (HR 0.518; 95% CI: 0.216-1.165).

"Endocrine therapy given in combination with a CDK4/6 inhibitor is a mainstay in ER+/HER2- metastatic breast cancer for first-line treatment. It is encouraging to see that patients with ESR1-mutations who had a longer duration of prior CDK4/6i therapy, when treated subsequently with elacestrant, had 8.6 months of median PFS versus 1.9 months with the standard of care, as we published at SABCS in December 2022. Until now, elacestrant’s potential benefit in patients with Non-Detected ESR1-mutations was an open question. The results presented at ASCO (Free ASCO Whitepaper) 2023, while exploratory, suggest that treatment with oral elacestrant following disease progression within six months of CDK4/6i treatment for Non-Detected ESR1-mutations may provide clinical benefit for these patients, and warrant further study," said Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center.

Safety data were consistent with previously reported results. Most adverse events (AEs), including nausea, were grade 1 and 2, and no grade 4 treatment-related AEs (TRAEs) were reported. Only 3.4% of patients receiving elacestrant and 0.9% receiving SOC discontinued therapy due to any TRAE. No deaths assessed as treatment-related were reported in either arm. No hematologic safety signal was observed, and none of the patients in either treatment arm had sinus bradycardia.

"At Menarini Group, we are focused on developing innovative solutions that address the greatest unmet needs in cancer treatments," said Elcin Barker Ergun, CEO of the Menarini Group. "ORSERDU represents an important step towards that, providing the first and only FDA-approved oral endocrine therapy after 20 years, for advanced or metastatic ER+/HER2- tumors with ESR1 mutations. This new data advances our understanding of further potential areas where elacestrant may help patients living with metastatic breast cancer who have limited treatment options."

2023 ASCO (Free ASCO Whitepaper) Annual Meeting Presentation Details
Abstract Title: Oral elacestrant vs standard-of-care in estrogen receptor-positive, HER2-negative (ER+/HER2-) advanced or metastatic breast cancer (mBC) without detectable ESR1 mutation (EMERALD): Subgroup analysis by prior duration of CDK4/6i plus endocrine therapy (ET)
Abstract #: 1070 | Poster Bd #: 291
Session Title: Breast Cancer – Metastatic
Session Date and Time: June 4, 2023; 8:00AM CDT, Hall A
Presentation Type: Poster

About the EMERALD Phase 3 Study (NCT03778931)

The EMERALD Phase 3 trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations. In the group of patients whose tumors had ESR1 mutations, elacestrant achieved a median PFS of 3.8 months vs 1.9 months on the SOC, and reduced the risk of progression or death by 45% (PFS HR=0.55, 95% CI: 0.39, 0.77) vs SOC.

About ORSERDU (elacestrant)

Indication

ORSERDU (elacestrant), 345 mg tablets, is approved by the U.S. Food & Drug Administration (FDA) for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Full prescribing information can be found at www.orserdu.com

Important Safety Information, ORSERDU

Warnings and Precautions

Dyslipidemia: Hypercholesterolemia and hypertriglyceridemia occurred in patients taking ORSERDU at an incidence of 30% and 27%, respectively. The incidence of Grade 3 and 4 hypercholesterolemia and hypertriglyceridemia were 0.9% and 2.2%, respectively. Monitor lipid profile prior to starting and periodically while taking ORSERDU.
Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, ORSERDU can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ORSERDU and for 1 week after the last dose.
Adverse Reactions

Serious adverse reactions occurred in 12% of patients who received ORSERDU. Serious adverse reactions in >1% of patients who received ORSERDU were musculoskeletal pain (1.7%) and nausea (1.3%). Fatal adverse reactions occurred in 1.7% of patients who received ORSERDU, including cardiac arrest, septic shock, diverticulitis, and unknown cause (one patient each).
The most common adverse reactions (≥10%), including laboratory abnormalities, of ORSERDU were musculoskeletal pain (41%), nausea (35%), increased cholesterol (30%), increased AST (29%), increased triglycerides (27%), fatigue (26%), decreased hemoglobin (26%), vomiting (19%), increased ALT (17%), decreased sodium (16%), increased creatinine (16%), decreased appetite (15%), diarrhea (13%), headache (12%), constipation (12%), abdominal pain (11%), hot flush (11%), and dyspepsia (10%).
Drug Interactions

Concomitant use with CYP3A4 inducers and/or inhibitors: Avoid concomitant use of strong or moderate CYP3A4 inhibitors with ORSERDU. Avoid concomitant use of strong or moderate CYP3A4 inducers with ORSERDU.
Use in Specific Populations

Lactation: Advise lactating women to not breastfeed during treatment with ORSERDU and for 1 week after the last dose.
Hepatic Impairment: Avoid use of ORSERDU in patients with severe hepatic impairment (Child-Pugh C). Reduce the dose of ORSERDU in patients with moderate hepatic impairment (Child-Pugh B).
The safety and effectiveness of ORSERDU in pediatric patients have not been established.
To report SUSPECTED ADVERSE REACTIONS, contact Stemline Therapeutics, Inc. at 1-877-332-7961 or via email at [email protected] or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The Marketing Authorization Application (MAA) is currently under review by the European Medicines Agency (EMA).

Elacestrant is also being investigated in several clinical trials in metastatic breast cancer disease, alone or in combination with other therapies: ELEVATE (NCT05563220); ELECTRA (NCT05386108); and ELCIN (NCT05596409). Elacestrant is also planned to be evaluated in early breast cancer disease.

The Menarini Group obtained global licensing rights for elacestrant in July 2020 from Radius Health, Inc. The Menarini Group is now fully responsible for global registration, commercialization, and further development activities for elacestrant.

On May 26, 2023 City of Hope, one of the largest cancer research and treatment organizations in the United States, reported that it would present research on promising treatments for blood, prostate and other cancers, as well as studies on germline testing for hereditary cancers and on reducing heart disease in childhood cancer survivors, at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s (ASCO) (Free ASCO Whitepaper) annual conference from June 2 to 6 in Chicago (Press release, City of Hope, MAY 26, 2023, View Source [SID1234632155]).

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!

More than 40,000 oncology professionals and others will attend the conference, or join virtually, to learn about the latest scientific research on cancer treatment, detection and prevention.

"This year’s ASCO (Free ASCO Whitepaper) Annual Meeting highlights the exceptional work City of Hope doctors and scientists are leading with the hope of finding better treatments against a wide range of cancers," said Steven T. Rosen, M.D., City of Hope provost and chief scientific officer, Irell & Manella Cancer Center Director’s Distinguished Chair. "Whether it’s working on our own immunotherapy trials for solid tumors, or partnering with companies to find novel medicines, City of Hope is committed to transforming cancer care for our patients and beyond."

City of Hope doctors and scientists will present oral and poster presentations on these and other abstracts:

Blood pressure medication shows promise in lowering heart failure risk for childhood cancer survivors

For people who were treated with anthracyclines — a class of chemotherapy drugs — for childhood cancers, heart failure can be a devastating side effect that develops later in life. To date, there have been no effective therapies to prevent heart failure in long-term childhood cancer survivors who have been treated with anthracyclines.

Now, Saro Armenian, D.O., M.P.H., City of Hope’s Barron Hilton Chair in Pediatrics, The Norman and Sadie Lee Foundation Professor in Pediatrics and director of the Division of Outcomes Research/Intervention, has led a Phase 2b clinical trial examining the effectiveness of a low-dose blood pressure medication called carvedilol to improve heart health in these survivors. The trial was double-blinded, meaning participants and doctors don’t know which therapy is received until the trial is over, creating less bias, and placebo-controlled, which refers to a group of participants receiving a treatment that has no active properties.

The trial was conducted at 30 sites and enrolled 182 participants to either receive low-dose carvedilol (12.5 mg/day) or a placebo.

Armenian and his team found that carvedilol was shown to be safe and effective in reversing early signs of heart injury during the two-year study period. Compared to the placebo arm, participants who took carvedilol had significantly better left ventricular chamber size and left ventricular end-systolic wall stress — two measurements of heart health — at two years.

"There are an estimated 500,000 long-term survivors of childhood cancer in U.S. alone and more than 40% will have been treated with anthracycline-based chemotherapies," said Armenian, who will give an oral presentation of the trial’s outcomes on Monday, June 5, at 9:12 a.m. CDT. "Our study is one of the first to demonstrate the safety and efficacy of a readily available heart failure prevention strategy in long-term survivors, setting the stage for optimizing cardiovascular outcomes in this growing population of survivors who will live for decades after their initial diagnosis."

Follow-up of participants is ongoing, which may inform the efficacy of the intervention beyond the two-year period. The team also has several research collaborations examining optimal strategies for remote patient monitoring for heart health in cancer survivors, which would allow real-time intervention prior to onset of irreversible cardiovascular injury.

"Remote monitoring options could bridge the gap in the community setting for at-risk patients by allowing point-of-care cardiac assessments by primary care providers to help track their heart health, or by facilitating home-based surveillance by specialized survivorship centers," Armenian said.

New treatment for relapsed or refractory leukemias performs well in first clinical trial

For patients with blood cancers that have returned or are treatment-resistant, the existing therapy options are few.

In an effort to expand treatment choices, Anthony S. Stein, M.D., associate director of City of Hope’s Gehr Family Center for Leukemia Research and professor with the Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, and a team of researchers are testing a new approach. Early results from the first-in-human study of SAR443579 (SAR’579) in relapsed or refractory acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia, or high-risk myelodysplasia have revealed positive results.

When activated, natural killer (NK) cells have innate cell killing function. SAR’579 is a trifunctional anti-CD123 NK cell engager which targets NK cells through CD16 and NKp46 and the tumor antigen CD123 on the AML cell. This co-engagement of the NK cells leads to an optimal activation resulting in tumor cell death.

In an oral presentation titled "A first-in-human study of CD123 NK cell engager SAR443579 in relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or high-risk myelodysplasia," being presented on Friday, June 2, at 2:24 p.m. CDT, Stein will outline findings from 23 AML patients in a Phase 1/2 clinical trial who received SAR’579, under development by Sanofi, to evaluate the treatment for safety, efficacy, and anti-leukemic activity. Patients received a median of two cycles for a median duration of seven weeks with escalating doses. The most common adverse events were infusion-related reactions and nausea.

"We found that SAR’579 was well-tolerated in heavily pretreated patients with refractory AML," Stein said. "In addition, we observed clinical benefits in the patients. Thirteen percent of all patients achieved a complete remission and 37.5 percent achieved a complete remission at the maximum highest dose of 1,000 micrograms per kilogram, once a week. These are encouraging findings for patients with AML."

The clinical trial is still open and continues to accrue patients. Stein and his team are working to define SAR’579’s optimal dose with the best safety and highest response profile.

Benefits of brexu-cel treatment for relapsed or refractory mantle cell lymphoma hold up in large, real-world study

Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T cell therapy and a Kite product. CAR T cell therapies use the body’s own cells, known as T cells, from the immune system to fight cancer.

Brexu-cel was first approved by the U.S. Food and Drug Administration in 2020 for relapsed or refractory (R/R) mantle cell lymphoma (MCL). Accelerated approval was granted based on a single-arm Phase 2 clinical trial called ZUMA-2. Now, an analysis led by Swetha Kambhampati, M.D., City of Hope assistant professor in the Division of Lymphoma, has shown the treatment to work well outside of the clinical trial.

Kambhampati and a team of researchers evaluated follow-up, updated data from 380 patients who participated in the ZUMA-2 trial and were also registered in the Center for International Blood and Marrow Transplant Research observational database. They found that at a median follow-up of 12 months, the objective response rate, or cancer diminishing, was 90%, and the complete response rate, which refers to the disappearance of all signs of cancer, was 78% with a median duration of response of 21.7 months. These results were comparable to those seen in the ZUMA-2 trial.

The team found that complete response rates were higher in patients who received brexu-cel in earlier lines of therapy, suggesting that treating R/R MCL patients with brexu-cel sooner may be beneficial. Kambhampati and others also examined outcomes based on prior treatment types and found them to be largely consistent in MCL patients who had received bruton tyrosine kinase inhibitors, a therapy that stops B cell growth to treat lymphoma, bendamustine (a type of chemotherapy), or autologous stem cell transplant therapy before taking brexu-cel.

"Our results show that brexu-cel has demonstrated efficacy and safety in the real-world setting in R/R MCL, regardless of prior therapy and it has improved efficacy when used in the earlier lines of therapy," said Kambhampati, who will give an oral presentation on the study on Tuesday, June 6, at 11:57 a.m. CDT. "But, it will be important to evaluate the durability of responses with brexu-cel in R/R MCL further with longer follow-up."

CAR T cell therapy tested in the treatment of metastatic castration-resistant prostate cancer patients

Chimeric antigen receptor (CAR)-engineered T cell therapies represent a recent and huge advance in cancer care for blood cancers and some brain tumors. Researchers are now looking to apply the approach to more solid tumors, which represent roughly 90% of all adult cancers.

CAR T therapies work by boosting the body’s own immune system to fight disease. Saul Priceman, Ph.D., associate professor in City of Hope’s Department of Hematology & Hematopoietic Cell Transplantation and associate director of Translational Sciences & Technologies in the T Cell Therapeutics Research Laboratory, and Tanya Dorff, M.D., City of Hope’s section chief, Genitourinary Disease Program, have been working to develop CAR T cell therapy for advanced prostate cancer.

Dorff will share results from a Phase 1 clinical trial using CAR T in metastatic, prostate stem cell antigen (PSCA)-positive, castration-resistant prostate cancer patients during a poster discussion on Saturday, June 3, starting at 1:15 p.m. CDT. (Metastatic refers to a cancer that has spread and castration-resistant refers to prostate cancer that keeps growing despite little to no testosterone, which is what usually causes prostate cancer to grow.)

Using a CAR T cell developed at City of Hope, Priceman, Dorff, and a team of researchers recruited 14 patients with PSCA-positive prostate cancer. PSCA is highly expressed in most prostate cancers and targeting PSCA with CAR T cell therapy has been previously shown to be potentially effective and feasible.

The team found that the PSCA-CAR T cell therapy had anti-cancer effects in these patients and more so in patients who had also received lymphodepletion (LD) chemotherapy. They also found that a lower dose of LD chemotherapy lessened the toxicity, or harmful effects, of the treatment without clear negative impact on CAR T expansion.

"More work needs to be done to optimize the use of CAR T cell therapy in prostate cancer since we are seeing occasional very deep responses, but not as many of them, or with as much durability, as we would like," Dorff said. "But we remain enthusiastic about the potential of this treatment. This study has pushed cellular immunotherapy one step closer to being a treatment option for advanced prostate cancer."

To further test the approach, the team will open a Phase 1b clinical trial with a new dosing strategy soon, which they believe will achieve greater efficacy with lower toxicity.

Universal germline testing could help identify people with hereditary breast-ovarian cancer syndrome to improve cancer control

Many people with hereditary breast-ovarian cancer syndrome (HBOC) and Lynch syndrome — caused by mutations in the genes, such as BRCA1, BRCA2, ATM, PALB2, and Lynch syndrome associated-genes — are unaware of their risk to develop cancer. While screening efforts catch about half of the people carrying these mutations, a better approach is needed.

City of Hope’s Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation (INSPIRE) study, led by Stephen Gruber, M.D., Ph.D., M.P.H., the Eva and Ming Hsieh Family Director’s Chair of the Center for Precision Medicine, Stanley Hamilton, M.D., professor and chair of the Department of Pathology, and Stacy W. Gray, M.D., professor and chief of the Division of Clinical Cancer Genomics and deputy director of the Center for Precision Medicine, hopes to be just that. The research project makes germline genetic testing available without charge to every participating City of Hope patient.

"Every mutation that is known to be associated with elevated cancer risk is actionable at some level," said Gray, who will be presenting data at ASCO (Free ASCO Whitepaper) from the INSPIRE study. "It could mean increased screenings to catch cancer at its earliest, most treatable stages, or risk-reducing surgery or new medications."

In a poster session on Saturday, June 3, from 1:15 to 4:15 p.m. CDT, Gray will outline recent findings from an informatics study aimed at determining whether genetic testing, through outreach like INSPIRE, leads to increased intervention for people carrying the BRCA mutation. By querying codified data, which refers to grouping data in meaningful categories, in City of Hope’s electronic data warehouse before and after germline testing, Gray and her study collaborators found that out of 217 patients whose testing revealed a known or likely BRCA mutation, 83% had procedures, imaging and/or therapy potentially related to the BRCA mutation.

"This suggests that universal genetic testing identifies patients who have inherited cancer risk who previously did not know their risk. Moreover, our study will evaluate whether individuals with BRCA and other actionable germline findings receive higher levels of relevant health care," Gray said. "However, this initial informatics approach is limited because key information on prior germline testing and motivations for surgery, such as whether a patient received a mastectomy as part of a treatment plan or chose one as a preventive measure, are not adequately captured in codified data."

She says that codified electronic health record queries will need to be augmented by text mining and/or manual chart review to fully capture care and assess the clinical utility of system-wide genetic care delivery interventions.

Given the promising findings of this initial work, Gray and the team are now evaluating care for the more than 17,000 patients who have enrolled in the INSPIRE study.

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]).

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!

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.

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 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]).

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 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.