On October 19, 2021 ImmunityBio, Inc. (NASDAQ: IBRX), a clinical-stage immunotherapy company, reported that Papillary disease (Cohort B), the second indication of its QUILT 3.032 Phase 2/3 study of intravesical BCG plus Anktiva in patients with BCG-unresponsive high-grade NMIBC (NCT03022825), also met its primary endpoints with disease-free survival of 57% of patients at 12 months (Press release, ImmunityBio, OCT 19, 2021, View Source [SID1234591515]). The company has previously reported that the primary endpoint of Cohort A, patients with CIS disease, has been met with a complete response of 72% (58/81).

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Non-muscle invasive bladder cancer (NMIBC) makes up 75%-85% of all bladder cancers in the U.S.; approximately 90% of NMIBC cases are papillary (stages Ta and T1). Current standard of care for high-grade papillary disease is intravesical BCG, with a 40% non-response rate.

To date, 73 patients have enrolled in Cohort B with a median follow-up of 17.3 months. The primary endpoint was met with a disease-free rate at 12-months of 57% (95% CI: 43.7%, 68.5%) and at 18-months, 53% (95% CI: 38.8%, 64.6%) by Kaplan-Meier analysis. Durable responses were noted in both cohorts and the therapy resulted in significant avoidance of cystectomy.

The safety profile of Anktiva (N-803) in Cohort B was consistent with that seen in Cohort A, which was recently presented at the American Urological Association’s 2021 Annual meeting, in which 0% SAEs, including 0% immune-related SAEs, were detected. In addition, 85% of the patients were able to avoid a cystectomy. A full analysis of efficacy and safety data for both Cohorts A (CIS) and B (Papillary) has been submitted to the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancer Symposium (ASCO GU), which is taking place in February 2022.

"Intravesical BCG has been the standard of care for more than 30 years for patients with non-invasive papillary tumors, yet, unfortunately some 40% of them don’t respond," said Patrick Soon-Shiong, M.D., Founder and Executive Chairman and Global Chief Scientific and Medical Officer of ImmunityBio. "Anktiva has demonstrated strong disease control in CIS, and based on the latest data from our study, it is showing the same effect in papillary tumors. This gives us confidence in the potential for all BCG-unresponsive NMIBC patients to benefit from this combination therapeutic."

The U.S. Patent & Trademark Office has recently allowed ImmunityBio’s patent application for a method of treating cancer, including non-muscle invasive bladder cancer, using Anktiva (N-803) in combination with Bacillus Calmette-Guerin (BCG). The new patent will extend patent life on the N-803/BCG combination therapy for bladder cancer to at least 2035.

The Urgent, Unmet Need to Treat NMIBC and Avoid Cystectomy

Bladder cancer has a high incidence worldwide; in 2020, an estimated 573,278 new cases were diagnosed and it was the cause of 212,536 deaths1. In the United States, bladder cancer is the fourth most commonly diagnosed solid malignancy in men and the twelfth for women and the American Cancer Society estimates there will be 83,730 new cases and 17,200 deaths from bladder cancer in 20212. Approximately 75–85% of patients with bladder cancer present with a disease that is confined to the mucosa [stage Ta, carcinoma in situ (CIS)] or submucosa (stage T1). These categories are grouped as non-muscle invasive bladder cancer (NMIBC). Of these, approximately 70% present as stage Ta, 20% as T1 and 10% as CIS3.

For the last 30 years, BCG immunotherapy has been the standard for treating NMIBC. However, disease recurrence and progression rates remain unacceptably high. Standard-of-care recommendations for these patients include lifetime invasive surveillance and rapid treatment of recurrences, creating a substantial financial burden and drastic impact on quality of life. Of those patients who experience recurrence, approximately 30% will progress and succumb to their disease over a 15-year period, and another 50% will undergo radical cystectomy of the bladder— a surgery to remove the entire bladder that may require removal of other surrounding organs—in an attempt to control their disease4.

Despite the advent of minimally invasive procedures and robotic techniques, the 90-day mortality and morbidity rates in patients who undergo cystectomy remain unacceptably high at 3-6% and 28-64%, respectively5 & 6. Based on this urgent need, FDA published guidance in February 2018 to address BCG unresponsive non-muscle invasive bladder cancer (NMIBC), stating that the goal of therapy in patients with BCG-unresponsive NMIBC is to avoid cystectomy.

About the Study and Breakthrough Designation

QUILT 3.032 is an open-label, three cohort, multicenter Phase 2/3 study of intravesical BCG plus Anktiva (N-803) in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) and was opened in 2017. The primary endpoint for Cohorts A (CIS with N-803+ BCG) and C (CIS with N-803 alone) of this Phase 2 study is incidence of complete response (CR) of CIS at any time and the primary endpoint for Cohort B (papillary) is 12-month disease-free rate. The FDA granted Fast Track Designation to the pivotal trial based on Phase I data. In December 2019, the FDA granted ImmunityBio Breakthrough Therapy Designation based on interim Phase 2 data indicating the primary endpoint of the trial was already met.

ImmunityBio’s IL-15 superagonist Anktiva (N-803)

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of the natural killer (NK) and T cells. N-803 is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. Its mechanism of action is direct specific stimulation of CD8+ T cells and NK cells through beta gamma T-cell receptor binding (not alpha) while avoiding T-reg stimulation. N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.

On October 19, 2021 Akoya Biosciences, Inc. (Nasdaq: AKYA) ("Akoya"), The Spatial Biology Company, reported that it will release financial results for the third quarter of 2021 after the market close on Monday, November 8th, 2021 (Press release, Akoya Biosciences, OCT 19, 2021, View Source [SID1234591511]). Company management will host a conference call to discuss financial results at 5:00 p.m. ET.

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Investors interested in listening to the conference call may do so by dialing (833) 562-0146 for domestic callers or (661) 567-1226 for international callers, followed by Conference ID: 6875504. A live and archived webcast of the event will be available on the "Investors" section of the Akoya website at View Source

On October 19, 2021 Cerus Corporation (Nasdaq: CERS) reported that its third quarter 2021 financial results will be released on Tuesday, November 2, 2021, after the close of the stock market (Press release, Cerus, OCT 19, 2021, View Source [SID1234591510]). The Company will host a conference call and webcast at 4:30 P.M. ET that afternoon, during which management will discuss the Company’s financial results and provide a general business overview and outlook.

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To listen to the live webcast and view the presentation slides, please visit the Investor Relations page of the Cerus website at View Source Alternatively, you may access the live conference call by dialing (866) 235-9006 (U.S.) or (631) 291-4549 (international).

A replay will be available on Cerus’ website, or by dialing (855) 859-2056 (U.S.) or (404) 537-3406 (international) and entering conference ID number 3970817. The replay will be available approximately three hours after the call through November 16, 2021.

On October 19, 2021 Clovis Oncology, Inc. (NASDAQ: CLVS) and ITM Isotope Technologies Munich SE, a leading radiopharmaceutical biotech company, reported the signing of a clinical supply agreement that provides Clovis Oncology with ITM’s therapeutic radioisotope no-carrier-added Lutetium-177 (n.c.a. 177Lu), EndolucinBeta, for use in the clinical development of FAP-2286, Clovis’ fibroblast activation protein (FAP)-targeting therapeutic candidate (Press release, Clovis Oncology, OCT 19, 2021, View Source [SID1234591509]). FAP-2286 is the first peptide-targeted radionuclide therapeutic (PTRT) candidate directed against fibroblast activation protein undergoing clinical testing and is currently being investigated in the Phase 1/2 LuMIERE study for patients with advanced solid tumors. The agreement covers an initial period of five years. Further details of the agreement were not disclosed.

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"Clovis Oncology is committed to advancing FAP-2286’s clinical development program and emerging as a leader in targeted radionuclide therapy. A critical element to advance this program is ensuring long-term supply of radioisotopes, and this agreement allows us to achieve that goal," said Patrick Mahaffy, President and CEO of Clovis Oncology. "In particular, we value ITM’s radiopharmaceutical expertise and global reach as we advance our targeted radionuclide therapy program into the clinic."

"This agreement underscores the potential of our n.c.a. Lutetium-177 to provide therapeutic value to patients with hard-to-treat tumors. Through our proprietary pipeline of Targeted Radionuclide Therapies and our agreements with other oncology leaders, we are establishing a new era of precision oncology treatments and we are happy to contribute to this exciting Clovis program," commented Steffen Schuster, CEO of ITM.

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting FAP. FAP is highly expressed by cancer-associated fibroblasts (CAFs) which are found in the majority of cancer types, but with limited expression in healthy fibroblasts, potentially making it a suitable target across a wide range of tumors. FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach medical radioisotopes, such as Lutetium-177 for therapeutic use, or Gallium-68 for imaging use.

ITM’s n.c.a. 177Lu (EndolucinBeta) is a high-purity version of the beta-emitting radioisotope Lutetium-177, that can be linked to a variety of tumor-specific targeting molecules for Targeted Radionuclide Therapy and has demonstrated significant anti-tumor effects in clinical and commercial use. ITM has developed a unique methodology to produce the highly pure form of Lutetium-177, without metastable Lutetium-177m, and manufactures n.c.a. 177Lu for development partnerships, distribution to clinics worldwide, and its own growing precision oncology pipeline.

In June 2021, Clovis initiated the Phase 1/2 LuMIERE clinical study of FAP-2286 in advanced solid tumors. The Phase 1 portion of the LuMIERE study (NCT 04939610) will evaluate the safety of the FAP-targeting investigational therapeutic agent and identify the recommended Phase 2 dose and schedule of Lutetium-177 labeled FAP-2286 (177Lu-FAP-2286), for which ITM will provide its n.c.a. 177Lu. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types.

About FAP-2286

FAP-2286 is a clinical candidate under investigation as a peptide-targeted radionuclide therapy (PTRT) and imaging agent targeting fibroblast activation protein (FAP). FAP-2286 consists of two functional elements; a targeting peptide that binds to FAP and a site that can be used to attach radioactive isotopes for imaging and therapeutic use. High FAP expression has been shown in pancreatic ductal adenocarcinoma, cancer of unknown primary, salivary gland, mesothelioma, colon, bladder, sarcoma, squamous non–small cell lung, and squamous head and neck cancers. High FAP expression was detected in both primary and metastatic tumor samples and was independent of tumor stage or grade. Clovis holds US and global rights for FAP-2286 excluding Europe, Russia, Turkey, and Israel.

FAP-2286 is an unlicensed medical product.

For more information about FAP-2286, Targeted Radionuclide Therapy (TRT), or Clovis’ TRT development program, CLICK HERE.

About n.c.a. Lutetium-177 / EndolucinBeta

No carrier-added Lutetium-177 (n.c.a. 177Lu) chloride, is a radiopharmaceutical precursor used in Targeted Radionuclide Therapy for the treatment of various diseases, like cancer. When labeled with a tumor-specific targeting molecule (e. g. peptide or antibody), the targeted radiopharmaceutical binds to a tumor-specific receptor, according to the lock and key principle. N.c.a. 177Lu has a half-life of 6.647 days and provides the highest specific activity of more than 3,000 GBq/mg at Activity Reference Time (ART). Optimal preconditions for efficient radiolabeling of biomolecules over its entire shelf-life of 9 days after production are ensured. N.c.a. 177Lu exhibits an extraordinary level of radionuclidic purity and does not contain metastable Lutetium-177m circumventing cost intensive clinical disposal management.

About Targeted Radionuclide Therapy

Targeted Radionuclide Therapy is an emerging class of cancer therapeutics, which seeks to deliver radiation directly to the tumor while minimizing delivery of radiation to normal tissue. Targeted radionuclide therapies are created by linking radioactive isotopes, also known as radionuclides, to targeting molecules (e.g., peptides, antibodies, small molecules) that can bind specifically to tumor cells or other cells in the tumor environment. Based on the radioactive isotope selected, the resulting agent can be used to image and/or treat certain types of cancer. Agents that can be adapted for both therapeutic and imaging use are known as "theranostics." Clovis, together with licensing partner 3B Pharmaceuticals, is developing a pipeline of novel, targeted radiotherapies for cancer treatment and imaging, including its lead candidate, FAP-2286, an investigational peptide-targeted radionuclide therapeutic (PTRT) and imaging agent, as well as three additional discovery-stage compounds. ITM is developing a proprietary precision oncology pipeline of targeted radiopharmaceuticals for diagnostics and treatment of a range of hard-to-treat cancer indications, such as neuroendocrine tumors, prostate cancer, glioblastoma, osteosarcoma and bone metastases, as well as folate receptor α positive tumors like lung, ovarian or breast cancer. Additionally, ITM supplies partners with its high-purity n.c.a. 177Lu for clinical and commercial development.

On October 19, 2021 AIM ImmunoTech Inc. (NYSE American: AIM) reported that it has submitted an Investigational New Drug application (IND) and an accompanying application for Fast Track status with the U.S. Food and Drug Administration (FDA) for a planned Phase 2 study of the company’s drug Ampligen as a therapy for locally advanced or metastatic late-stage pancreatic cancer (Press release, AIM ImmunoTech, OCT 19, 2021, View Source [SID1234591508]).

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The planned AMP-270 clinical trial of approximately 250 subjects will be a Phase 2, randomized, open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen when added to SOC (standard of care) versus SOC alone for subjects with advanced pancreatic carcinoma recently treated with FOLFIRINOX chemotherapy regimen. Secondary objectives include comparing safety and tolerability.

Amarex Clinical Research will manage the AIM-sponsored study. The Buffett Cancer Center at the University of Nebraska Medical Center (UNMC) and Erasmus MC in The Netherlands are expected to be the primary study sites, although additional sites are anticipated.

Key support for both the study and the application for Fast Track status includes statistically significant clinical data in an Erasmus MC early-access program of 27 subjects where the overall survival of the Ampligen-treated cohort was 19.2 months from the start of FOLFIRINOX, compared to 12.5 months in the historical control group, for an increase in survival of 6.7 months. Additionally, several subjects are still alive more than three years later.

AIM believes that the clinical significance of these data as a treatment for pancreatic cancer provide Ampligen with a strong case for FDA Fast Track designation, which is designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill unmet medical needs. A drug that has been granted FDA Fast Track status is eligible for some or all of the following:

More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA
AIM Chief Scientific Officer David Strayer, MD, commented, "Given the extensive work to date, we are well positioned to move aggressively and launch the Phase 2 trial of Ampligen upon approval of the IND. We could not be more enthusiastic about the outlook for this program given the compelling prior clinical data from Erasmus MC, which demonstrated a significant improvement in median overall survival, compared to a matched historical control group. Ampligen has also demonstrated a strong safety profile in numerous trials. At the same time, we are excited to have submitted our Fast Track application, which would confer a number of important benefits and potentially help accelerate approval."

AIM CEO Thomas K. Equels further commented, "Submission of our IND and Fast Track application are very significant milestones for the company and I would like to thank our entire team, as well as our clinical and regulatory advisors, for their tremendous efforts in preparing these carefully planned submissions. The rapid progress we have made is especially important given the devastating nature of pancreatic cancer. Further, both the FDA and the EMA have granted Ampligen orphan drug status in pancreatic cancer. This creates the potential for several years of market exclusivity. There is a significant unmet need for a safe and effective therapy for these patients, and we believe Ampligen holds enormous promise."

See:

AIM ImmunoTech Inc.’s Drug Ampligen Awarded FDA’s Orphan Drug Designation Status for the Treatment of Pancreatic Cancer
AIM ImmunoTech’s Subsidiary Receives Orphan Medicinal Product Designation by the European Medicines Agency for Ampligen to Treat Pancreatic Cancer