On October 2, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported a clinical trial collaboration agreement with AstraZeneca (LSE/STO/Nasdaq: AZN) to evaluate casdatifan (AB521), Arcus’s investigational HIF-2a inhibitor, in combination with volrustomig, AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, in patients with ccRCC (Press release, Arcus Biosciences, OCT 2, 2024, View Source [SID1234647009]).

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"We believe casdatifan has best-in-class potential, based on the observed PK and PD profiles and the emerging clinical data from our ARC-20 study in patients with ccRCC," said Terry Rosen, Ph.D., chief executive officer of Arcus. "This agreement will enable Arcus and AstraZeneca to collaborate and assess the potential for the novel combination of casdatifan with volrustomig to improve outcomes for patients with ccRCC."

"Renal cell carcinoma is a known CTLA-4-responsive tumor type, and our first-in-human study with volrustomig monotherapy demonstrated encouraging efficacy in first-line advanced ccRCC," said Cristian Massacesi, chief medical officer and oncology chief development officer, AstraZeneca. "We are excited by the potential to build on this by combining HIF-2a inhibition with volrustomig to drive deeper and more durable responses for patients."

As part of this collaboration, AstraZeneca will sponsor and operationalize a study to evaluate the safety and early efficacy of the casdatifan plus volrustomig combination in patients with advanced ccRCC.

This is the second clinical collaboration between Arcus and AstraZeneca. In 2020, the companies announced a clinical collaboration for PACIFIC-8, a registrational Phase 3 study of domvanalimab, an Fc-silent anti-TIGIT antibody, added to backbone global standard-of-care durvalumab, an anti-PD-L1 antibody, in patients with unresectable Stage III non-small cell lung cancer.

Under the Gilead and Arcus collaboration agreement, Gilead has the right to opt-in to development and commercialization for casdatifan after Arcus’s delivery of a qualifying data package.

About Casdatifan (AB521)

Casdatifan is a small-molecule inhibitor of HIF-2a, a transcription factor involved in oxygen sensing in multiple organs as well as in tumors. Clear cell RCC is almost universally associated with HIF-2a dysregulation as a result of genetic abnormalities in the VHL pathway. This creates a situation of pseudohypoxia and the abnormal increase in HIF-2a-mediated expression of a wide array of proteins involved in cancer cell proliferation and survival, treatment resistance and angiogenesis. Casdatifan is being evaluated in ARC-20, a Phase 1/1b study in cancer patients, and STELLAR-009, a Phase 1b/2 study in combination with zanzalintinib in patients with advanced solid tumors, including ccRCC.

Casdatifan and domvanalimab are investigational molecules. Approval from any regulatory authority for any use of these molecules globally has not been received, and their safety and efficacy have not been established.

About RCC

According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 81,600 Americans will be diagnosed with kidney cancer in 2024. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 15%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment.

On October 2, 2024 TerSera Therapeutics LLC reported the presentation of new real-world analyses on the treatment patterns of goserelin in women with breast cancer (Press release, TerSera Therapeutics, OCT 2, 2024, View Source [SID1234647010]). The data were presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Quality Care Symposium, held September 27th and 28th in San Francisco, CA.

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The goal of this study was to demonstrate the characteristics of US patients with a diagnosis of breast cancer treated with either goserelin 3.6 mg or 10.8 mg and analyze goserelin treatment patterns using real-world evidence (RWE). This retrospective study used US electronic health record data through TriNetX, a global healthcare research network. The study included adult women with a history of breast cancer and with ≥2 prescriptions of goserelin between January 2017 – December 2022. Follow-up occurred until March 15, 2024.

Overall, 3,620 patients were identified: 2,870 treated with goserelin 3.6 mg, 410 with goserelin 10.8 mg, and 340 who switched from goserelin 3.6 mg to 10.8 mg. Patient demographics, treatment adherence, and healthcare resource utilization (HCRU) were examined and summarized using descriptive analytics.

"For young women with hormone-sensitive breast cancer at high-risk of relapse, suppression of ovarian function is an essential component of their long-term treatment plan," said Lonnie Brent, Pharm.D., Senior Vice President, Medical and Scientific Affairs for TerSera. "This real-world evidence presented at the ASCO (Free ASCO Whitepaper) Quality Care Symposium increases our understanding of the current treatment patterns for young women with breast cancer receiving goserelin."

U.S. INDICATIONS

ZOLADEX 3.6 mg and ZOLADEX 10.8 mg are indicated for:

Management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate in combination with flutamide. Treatment with ZOLADEX and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy.
Palliative treatment of advanced carcinoma of the prostate.
ZOLADEX 3.6 mg is also indicated for:

Management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy. Experience with ZOLADEX for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months.
Use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding.
Palliative treatment of advanced breast cancer in pre- and perimenopausal women.
IMPORTANT SAFETY INFORMATION

Anaphylactic reactions to ZOLADEX have been reported in the medical literature. ZOLADEX is contraindicated in patients with a known hypersensitivity to GnRH, GnRH agonist analogues, or any of the components in ZOLADEX.

ZOLADEX is contraindicated during pregnancy unless used for palliative treatment of advanced breast cancer. ZOLADEX can cause fetal harm when administered to a pregnant woman. If used during pregnancy, the patient should be apprised of the potential hazard to the fetus. There is an increased risk for pregnancy loss due to expected hormonal changes that occur with ZOLADEX treatment. ZOLADEX should not be given to women with undiagnosed abnormal vaginal bleeding.

Pregnancy must be excluded for use in benign gynecological conditions. Women should be advised against becoming pregnant while taking ZOLADEX. Effective nonhormonal contraception must be used by all premenopausal women during ZOLADEX therapy and for 12 weeks following discontinuation of therapy.

Transient worsening of tumor symptoms, or the occurrence of additional signs and symptoms of breast cancer, may occasionally develop during the first few weeks of treatment. Some patients may experience a temporary increase in bone pain. Monitor patients at risk for complications of tumor flare.

Hyperglycemia and an increased risk of developing diabetes or worsening of glycemic control in patients with diabetes have been reported in men receiving GnRH agonists like ZOLADEX. Monitor blood glucose levels and glycosylated hemoglobin (HbA1c) periodically and manage according to current clinical practice.

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists like ZOLADEX in men. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Hypercalcemia has been reported in some breast cancer patients with bone metastases after starting treatment with ZOLADEX. If hypercalcemia does occur, appropriate treatment measures should be initiated.

Hypersensitivity, antibody formation and acute anaphylactic reactions have been reported with GnRH agonist analogues.

ZOLADEX may cause an increase in cervical resistance. Therefore, caution is recommended when dilating the cervix for endometrial ablation.

GnRH agonists may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Injection site injury and vascular injury including pain, hematoma, hemorrhage and hemorrhagic shock, requiring blood transfusions and surgical intervention, have been reported with ZOLADEX. Extra care should be taken when administering ZOLADEX to patients with low BMI and/or to patients receiving full dose anticoagulation.

Depression may occur or worsen in women receiving GnRH agonists.

Treatment with ZOLADEX may be associated with a reduction in bone mineral density over the course of treatment. Data suggest a possibility of partial reversibility. In women, current available data suggest that recovery of bone loss occurs on cessation of therapy in the majority of patients.

In women, the most frequently reported adverse reactions were related to hypoestrogenism. The adverse reaction profile was similar for women treated for breast cancer, dysfunctional uterine bleeding, and endometriosis.

The most commonly reported adverse reactions with ZOLADEX in clinical trials for endometriosis were: hot flashes (96%), vaginitis (75%), headache (75%), decreased libido (61%), emotional lability (60%), depression (54%), sweating (45%), acne (42%), breast atrophy (33%), seborrhea (26%), and peripheral edema (21%).

The most commonly reported adverse reactions with ZOLADEX in clinical trials for endometrial thinning were: vasodilation/hot flashes (57%), headache (32%), sweating (16%), and abdominal pain (11%).

The most commonly reported adverse reactions with ZOLADEX in breast cancer clinical trials were hot flashes (70%), decreased libido (47.7%), tumor flare (23%), nausea (11%), edema (5%), and malaise/fatigue/lethargy (5%). Injection site reactions were reported in less than 1% of patients.

For ZOLADEX 3.6 mg: Hot flashes (62%), sexual dysfunction (21%), decreased erections (18%), lower urinary tract symptoms (13%), lethargy (8%), pain (worsened in the first 30 days) (8%), edema (7%), upper respiratory infection (7%), rash (6%), and sweating (6%).

For ZOLADEX 10.8 mg: Hot flashes (64%), pain (general) (14%), gynecomastia (8%), pelvic pain (6%), and bone pain (6%).

In the locally advanced carcinoma of the prostate clinical trial, additional adverse event data were collected for the combination therapy with radiation group during both the hormonal treatment and hormonal treatment plus radiation phases of this study. Adverse experiences (incidence >5%) in both phases of this study were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%). Treatment with ZOLADEX and flutamide did not add substantially to the toxicity of radiation treatment alone.

Please see Full Prescribing Information for ZOLADEX 3.6 mg and ZOLADEX 10.8 mg.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit fda.gov/safety/medwatch or call 1-800-FDA-1088. You can also contact TerSera Therapeutics at 1-844-334-4035 or [email protected].

About HR-positive breast cancer

Breast cancer is the second most commonly diagnosed cancer and one of the leading causes of cancer-related deaths worldwide. 2 In the United States, over 310,000 women will be diagnosed with breast cancer this year; 40,000 will be under the age of 50. 3 Approximately 75% of diagnosed cases in women under age 50 are considered to be hormone positive (HR+) breast cancer. Compared to older women, young women generally face more aggressive cancers and lower survival rates.4,5 Recent studies have shown that breast cancer before age 40 differs biologically from the cancer faced by older women.6

About ZOLADEX (goserelin implant)

ZOLADEX is an injectable luteinizing hormone-releasing hormone agonist (LHRHa) used to treat prostate cancer, breast cancer, and certain benign gynecological disorders. First approved in the U.S. in 1989, ZOLADEX is available as a 3.6 mg implant dosed every 28 days or as a 10.8 mg implant dosed every 12 weeks. Worldwide, ZOLADEX 3.6 mg is approved for use in breast cancer in 125 countries. ZOLADEX 10.8 mg is approved for use in breast cancer in over 60 countries.

On October 1, 2024 IN8bio, Inc. (Nasdaq: INAB), a leading clinical-stage biopharmaceutical company focused on innovative gamma-delta T cell therapies, reported that it has entered into a definitive securities purchase agreement with accredited investors for a private placement that is expected to result in gross proceeds of approximately $12.4 million to IN8bio, before deducting placement agent fees and other offering expenses (Press release, In8bio, OCT 1, 2024, View Source [SID1234646978]). The net proceeds from this financing are expected to fund the Company’s current operating plan into 2026.

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The private placement was led by an existing healthcare-focused institutional investor and included a large mutual fund company and other existing and new institutional investors.

Under the terms of the securities purchase agreement, the Company will sell units comprised of an aggregate of 25,759,595 shares of the Company’s common stock, par value $0.0001 per share, pre-funded warrants to purchase 5,646,853 shares of common stock and warrants to purchase up to 31,406,448 shares of common stock (the "Series C Warrants"). The units will be sold at a purchase price of $0.395 per unit (or $0.3949 per unit with respect to units that include pre-funded warrants in lieu of common stock). The pre-funded warrants will have an exercise price of $0.0001 per share. The Series C Warrants will have an exercise price of $0.27 per share.

IN8bio intends to use the net proceeds from the private placement to fund the clinical development of INB-100 and future product candidates and for working capital and other general corporate purposes. The proceeds will support the continued enrollment of patients in the expansion cohort with a new target total enrollment of approximately 25 patients at the recommended Phase 2 dose. IN8bio expects to complete this additional enrollment in the first half of 2025, with long-term follow-up results anticipated in late 2025 and in 2026. To affirm the improvements in relapse free and overall survival observed to date and to further de-risk a future registrational randomized control trial, IN8bio will also seek to add a parallel control cohort to prospectively assess leukemia patients and enable comparison between patients receiving INB-100 to those who only receive standard haplotransplantation.

The closing of the private placement is subject to customary closing conditions and is expected to occur on or about October 4, 2024.

Newbridge Securities Corporation acted as the sole placement agent for the private placement.

The offer and sale of the foregoing securities is being made in a private placement pursuant to an exemption under the Securities Act of 1933, as amended (the "Securities Act"), and the Securities have not been registered under the Securities Act or applicable state securities laws. The Securities may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and applicable state securities laws.

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

On October 1, 2024 Kiromic BioPharma, Inc. (OTCQB: KRBP) ("Kiromic" or the "Company") reported good safety and favorable ongoing efficacy results from the 10-month follow-up visit of the first patient treated in its Deltacel-01 Phase 1 clinical trial (Press release, Kiromic, OCT 1, 2024, View Source [SID1234646980]). This trial is evaluating Deltacel (KB-GDT-01), the Company’s allogeneic, off-the-shelf, Gamma Delta T-cell (GDT) therapy, in patients with stage 4 metastatic non-small cell lung cancer (NSCLC) who have failed to respond to standard therapies.

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In this patient, the tumor size was reduced by approximately 27% compared with the pre-treatment size, and no new sites of disease were identified. As a result, the progression-free survival (PFS) has reached 10 months with no reported adverse events. These results follow an approximate 20% reduction in tumor size detected at eight months post-treatment and an approximate 13% reduction at six months post-treatment. This patient is being treated at the Beverly Hills Cancer Center (BHCC).

"As this patient is the most advanced in our ongoing Deltacel-01 clinical trial, we are particularly encouraged by these latest follow-up results that continue to validate the potential of Deltacel as a safe and effective treatment for patients with later-stage cancers," said Pietro Bersani, Chief Executive Officer of Kiromic BioPharma. "We believe these findings underscore the promise of our allogeneic GDT therapy in providing durable clinical benefit."

"The latest results from this patient are highly promising, particularly given the durable progression-free survival and tumor reduction we observed," said Afshin Eli Gabayan, M.D., Medical Oncologist, Medical Director and Deltacel-01 Principal Investigator at BHCC. "This patient’s response to Gama Delta T-Cell Treatment continues to provide optimism as we evaluate Deltacel’s therapeutic potential. Continued meaningful results could represent a significant breakthrough for these late-stage cancer patients with limited treatment options."

Kiromic expects to report additional follow-up results from the fourth patient enrolled in this study in October.

About Deltacel-01

In Kiromic’s open-label Phase 1 clinical trial, titled "Phase 1 Trial Evaluating the Safety and Tolerability of Gamma Delta T Cell Infusions in Combination With Low Dose Radiotherapy in Subjects With Stage 4 Metastatic Non-Small Cell Lung Cancer" (NCT06069570), patients with stage 4 NSCLC will receive two intravenous infusions of Deltacel with four courses of low-dose, localized radiation over a 10-day period. The primary objective of the Deltacel-01 trial is to evaluate safety, while secondary measurements include objective response, progression-free survival, overall survival, time to progression, time to treatment response and disease control rates.

On October 1, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the completion of the acquisition of CN201 from Curon Biopharmaceutical (Curon), a novel investigational clinical-stage bispecific antibody for the treatment of B-cell associated diseases (Press release, Merck & Co, OCT 1, 2024, View Source [SID1234646981]).

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"By actively depleting B-cells, CN201 offers applications spanning both B-cell malignancies and autoimmune diseases. We look forward to building upon the foundational work started by the Curon team," said Dr. Dean Y. Li, president, Merck Research Laboratories.

CN201 is currently being investigated in Phase 1 and Phase 1b/2 clinical trials for the treatment of patients with relapsed or refractory non-Hodgkin’s lymphoma (NHL) and relapsed or refractory B-cell acute lymphocytic leukemia (ALL), respectively. Preliminary data suggest CN201 has activity in patients with relapsed or refractory B-cell hematologic malignancies and is well tolerated, potentially leading to significant and sustained reductions in B-cell populations.

Transaction details

Under the agreement, Merck, through a subsidiary, has acquired full global rights to CN201. As previously disclosed, the transaction is being accounted for as an asset acquisition. Merck is recording a pre-tax charge of approximately $750 million (reflecting the upfront payment and other related costs), or approximately $0.28 per share, which will be included in third-quarter non-GAAP results and was not included in Merck’s full-year financial outlook issued on July 30. As a matter of policy, Merck provides updates to its financial outlook once each quarter and will provide an update to its full-year financial outlook when it reports third-quarter 2024 results on October 31.

About CN201

CN201 is a novel CD3xCD19-targeting T-cell-engager bispecific antibody, designed to target B cells for elimination by T cells. CN201 is currently being evaluated in Phase 1 and Phase 1b/2 clinical trials for the treatment of relapsed or refractory non-Hodgkin’s lymphoma and relapsed or refractory acute lymphocytic leukemia, respectively.