On November 10, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported data for CTX130 for the treatment of relapsed or refractory renal cell carcinoma (RCC) as an oral presentation delivered by City of Hope’s Sumanta Pal, M.D. Additionally, together with collaborators at the Moffitt Cancer Center, the Company presented preclinical data in a poster presentation demonstrating the potential of potency-enhanced anti-CD83 CAR-T cells in preventing relapse in acute myeloid leukemia (AML) (Press release, CRISPR Therapeutics, NOV 10, 2022, View Source [SID1234623733]).

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"We are very pleased by the encouraging data from our first-in-human clinical trial exploring CD70-targeting CAR-T cell therapy in clear cell RCC. In this trial, treatment with CTX130 resulted in a durable complete response, and the trial demonstrated a favorable disease control rate overall. We remain excited by the results presented today for the CTX130 trial for the treatment of relapsed or refractory RCC," said Phuong Khanh (P.K.) Morrow, M.D., FACP, Chief Medical Officer of CRISPR Therapeutics. "Additionally, we presented a poster highlighting preclinical data that demonstrates that CRISPR-edited allogenic anti-CD83 CAR-T cells show potent activity in models of AML and can be a promising CAR-T target for the treatment of AML."

"At present, a treatment that offers patients with advanced kidney cancer the possibility of a durable remission with limited toxicity remains elusive. Our data shared today show encouraging activity for an allogeneic CAR-T therapy in this setting and highlights the potential of this modality for these patients," added Sumanta Pal, M.D., Professor, Department of Medical Oncology and Therapeutics Research, Co-director, Kidney Cancer Program, and medical oncologist at City of Hope, one of the largest cancer research and treatment organizations in the United States.

Key details and takeaways from the oral presentation and poster include:

Title: CTX130 allogeneic CRISPR-Cas9–engineered chimeric antigen receptor (CAR) T cells in patients with advanced clear cell renal cell carcinoma: Results from the Phase 1 COBALT-RCC study
Abstract Number and Type: 558, oral presentation
Session Number: 113, Cellular Therapies + Bispecifics
Date and Time: Thursday, November 10, 2022, 5:37 PM ET

This first-in-human clinical trial exploring CD70-targeting CAR-T cell therapy in clear cell RCC (ccRCC) showed a tolerable safety profile with no off-target toxicities and encouraging antitumor activity.
One patient experienced a durable complete response, the first to be achieved with allogeneic CAR-T cell therapy in patients with relapsed/refractory solid tumors.
CTX130 achieved a 77% disease control rate in a heavily pretreated RCC patient population. The longest duration of stable disease achieved was observed for 7.8 months and ongoing at the time of data cutoff. During periods of stable disease, patients did not receive any other anticancer therapies.
The results from the COBALT-RCC study represent a clinically meaningful proof-of-concept for further exploration of CD70-targeting CAR-T cells in ccRCC and other CD70+ malignancies.
A next generation anti-CD70 CAR-T program (CTX131) is being developed, which incorporates the edits in CTX130 with additional edits to the Regnase-1 and TGFBR2 genes. These additional edits have been shown to significantly increase potency of the CAR-T cells in preclinical models.
Title: CRISPR/Cas9 gene-edited, allogeneic anti-CD83 CAR-T cells demonstrate potent activity in GvHD and AML tumor models
Abstract Number and Type: 367, poster
Date and Time: Thursday, November 10, 2022, 9:00 AM – 9:00 PM ET

CD83 is a promising CAR-T target for the treatment of AML.
While anti-CD83 CAR-T cells show encouraging activity alone, that activity can be improved through a variety of means, including knock out of CD83 to prevent CAR-mediated fratricide, knock out of B2M to reduce allogeneic rejection, and combination with belatacept.
CRISPR/Cas9-mediated disruption of Regnase-1 and TGFBR2 expression further improves potency and survival in AML models in vivo.
The presentations are available for viewing at View Source

On November 10, 2022 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), reported new appointments to the leadership team, reported its financial results for the quarter ended September 30, 2022 and provided a business update (Press release, Phio Pharmaceuticals, NOV 10, 2022, View Source [SID1234623732]). Phio is a clinical stage biotechnology company whose proprietary INTASYL technology makes immune cells more effective in killing tumor cells. INTASYL is the only self-delivering RNAi technology focused on immuno-oncology therapeutics.

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The continuing enrollment in its first-in-human clinical study of PH-762 for advanced melanoma, along with recent positive data from four of its preclinical studies, has attracted new and industry-experienced executives to the Company. The new leadership team will join the current executive team to move the Company forward as it evolves its proprietary platform, INTASYL, from discovery to development.

The newly expanded leadership team is led by industry veteran Robert Bitterman, a member of the board of directors since 2012. Appointed Executive Chairman in September of this year, he assumed the duties leading all aspects of the Company’s operations. Mr. Bitterman brings 25 years of executive leadership experience in the pharmaceutical and biologic life science industry. He also has prior experience in senior financial and investor relations roles.

A key part of this new leadership team includes the appointment of Linda Mahoney as Vice President of Project Development, where she will lead the coordination of a multifunctional team to advance INTASYL compounds through the clinical development process. Ms. Mahoney is a pharmaceutical development executive with more than 25 years of experience in the industry. Previously, Ms. Mahoney was Vice President of Scientific Operations and Business Development at Cutanea Life Sciences, Inc. She also held positions in project management, product development and commercial supply chain at Sanofi-Aventis. Ms. Mahoney led numerous cross-functional pharmaceutical project teams through all stages of development, from product concept through commercialization.

Supporting the leadership team through the clinical development process is Dr. Mary Spellman, a board-certified dermatologist. Dr. Spellman will be working with the Company as a medical advisor and clinical development consultant. Dr. Spellman recently served as Chief Medical Officer at Castle Creek Biosciences, and prior to that at Menlo Therapeutics. She has contributed to the initiation of numerous Investigational New Drug applications, and to multiple drug and biologic marketing applications in a spectrum of clinical indications. Dr. Spellman is a Fellow of the American Academy of Dermatology, and currently is President of the Dermatologists in Industry organization. She is a former Associate Editor and now is a Reviewer for the Journal of the American Academy of Dermatology.

Phio’s business development activities will be supplemented by Michael Cozart, Managing Partner at LifeSci Consulting, LLC, a global strategy, consulting, and transaction advisory firm.

Recent Corporate Updates

Phio’s research partner, Helmholtz Munich, presented preclinical data on Phio’s lead clinical product PH-762, an INTASYL compound targeting PD-1, at the 9th Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (ITOC) annual meeting. PH-762 demonstrated increases in T cell population expressing stem-cell like characteristics. This increase in T cell population is expected to improve T cell persistence in vivo, therefore, resulting in enhanced duration of anti-tumor activity.
At the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), Phio presented four posters demonstrating anti-tumor activity in preclinical models with our INTASYL compounds silencing the proteins BRD4, CTLA4, TIGIT and CTGF. Also, in preparation for an upcoming clinical trial in collaboration with our partner AgonOx, Inc., a poster demonstrating ability to manufacture clinical scale grade TIL with and without PH-762, our INTASYL compound targeting PD-1 was presented. An additional poster reported on the clinical trial design and update on the enrollment in our Phase 1b study of PH-762 for the treatment of advanced melanoma.
Upcoming Pipeline Milestones

Plans to initiate a clinical trial evaluating the use of PH-762 and DP TIL in ACT during the fourth quarter of 2022 in partnership with AgonOx, Inc.
Expects to finalize IND-enabling studies for PH-894 by year end 2022
Expects to report top-line data from the first group of subjects with advanced melanoma in the clinical trial for PH-762 in the first quarter of 2023
Additional data publications on the Company’s pipeline programs
Financial Results

Cash Position

At September 30, 2022, the Company had cash of $14.5 million as compared with $24.1 million at December 31, 2021. The Company expects its current cash will be sufficient to fund currently planned operations for at least the next 12 months.

Research and Development Expenses

Research and development expenses decreased 6% to approximately $2.5 million for the quarter ended September 30, 2022, compared with approximately $2.7 million for the quarter ended September 30, 2021. The decrease in research and development expenses was primarily due manufacturing costs for PH-762 and PH-894 and the preclinical studies required for the Company’s PH-762 intratumoral clinical trial that were incurred in the prior year period offset by increases in research and development expenses for the preclinical studies required for the Company’s planned clinical trial with PH-894 conducted in the current year period.

General and Administrative Expenses

General and administrative expenses were approximately $1.1 million for the quarters ended September 30, 2022 and 2021 and were consistent quarter over quarter.

Net Loss

Net loss decreased 4% to approximately $3.6 million, or $0.26 per share, for the quarter ended September 30, 2022, compared with $3.7 million, or $0.28 per share, for the quarter ended September 30, 2021. The decrease in net loss was primarily attributable to the decrease in research and development expenses as described above.

About INTASYL

INTASYL is the only self-delivering RNAi technology focused on immuno-oncology therapeutics. INTASYL compounds are chemically modified siRNA’s that provide efficient, spontaneous cellular uptake and potent, long lasting intracellular activity targeting a broad range of cell types and tissues. INTASYL drugs precisely target specific proteins that reduce the body’s ability to fight cancer, without the need for specialized formulations or drug delivery systems. In comparison to biologics and cell and gene therapies, INTASYL has a favorable non-clinical toxicity and safety profile, and a streamlined chemical synthesis that reduces costs and offers substantial convenience to the prescriber and patient.

PH-762 is an INTASYL compound that reduces the expression of PD-1, a protein that inhibits T cells’ ability to kill cancer cells. By suppressing PD-1, the T cells are re-activated to kill cancer cells. PH-762 is being developed as a standalone drug therapy (Direct-to-Tumor) and also in combination with adoptive cell therapy. PH-762 is in a Phase 1b study for the treatment of advanced melanoma.

PH-894 is an INTASYL compound that silences BRD4, a protein that controls gene expression in both T cells and tumor cells, thereby effecting the immune system as well as the tumor. What sets this compound apart is its dual mechanism: INTASYL PH-894 suppression of BRD4 in T cells results in T cell activation; additionally, suppression of BRD4 in tumor cells results in tumors becoming more sensitive to T-cell killing.

PH-804 is an INTASYL compound that targets TIGIT, a protein that inhibits the activity of Natural Killer (NK) cells. A recent study demonstrated that NK cells, when treated with PH-804, increased activation and enhanced the ability of NK cells to kill cancer cells.

On November 10, 2022 Vaccitech plc (NASDAQ: VACC) reported its financial results for the third quarter ended September 30, 2022 and provided an overview of the Company’s recent corporate developments (Press release, Vaccitech, NOV 10, 2022, View Source [SID1234623731]). Vaccitech is a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases, autoimmunity, and cancer.

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"This has been a very exciting quarter at Vaccitech. During the past three months we have made significant progress on our clinical programs, strengthened our balance sheet and leadership team, and continued to actively engage with investors," remarked Bill Enright, CEO of Vaccitech. "We dosed the first patient in our Phase 2b clinical trial of VTP-300 in HBV and reported the findings of our Phase 1b/2a study of VTP-300 at the American Association for the Study of Liver Disease (AASLD) Liver meeting. In addition, we published a paper in Cell showing the activation of two key pathways with intravenous (IV) vaccination of a SNAPvax construct, which led to improved T cell mediated tumor killing in a pre-clinical model. We were also very pleased to announce the promotion of Gemma Brown to the role of CFO. I would also like to note that that this quarter’s royalty and milestone payments from the sales of Vaxzervria, AstraZeneca’s COVID-19 vaccine, have assisted in extending our cash runway into the first quarter of 2025. All told, this was a very active quarter for us, and we look forward to continuing our progress and outreach in the coming quarter and year."

"We have made excellent progress in our clinical programs in the past quarter and expect to reach a number of important clinical milestones in 2023," stated Dr. Meg Marshall, Chief Medical Officer of Vaccitech. "We expect to have initiated our Phase 1/2a clinical study in the fourth quarter of 2022 with the first patient first visit (FPFV) for VTP-850, our prostate cancer program, early in the first quarter of 2023, and FPFV for VTP-1100, our HPV-Cancer program, early in the third quarter of next year. FPFV for VTP-1000, our program in Celiac disease, is slated for the fourth quarter of 2023. We also plan to present data from multiple ongoing studies of VTP-300 in HBV next year as well. So, we are looking forward to a 2023 filled with exciting clinical advances."

Third Quarter 2022 Financial Highlights

·Cash position: As of September 30, 2022, cash and cash equivalents were $200.1 million, compared to $214.1 million as of December 31, 2021. The cash burn from operating activities was $43.9 million, being the net of R&D and G&A spend offset by the cash received from revenue recognized in respect of sales of Vaxzevria. $5.2 million of net cash was used in investing activities, which includes the buildout of the state of the art laboratory and Corporate Headquarters in Harwell, United Kingdom, where the Company relocated in the third quarter of 2022.

·Revenues: Revenues comprised primarily of the Company’s share of milestone and royalty payments received by OUI from AstraZeneca related to commercial sales of Vaxzevria. Revenues were $6.2 million in the third quarter of 2022 compared to $17.1 million in the second quarter of 2022, with the reduction attributable to no milestones being achieved in the third quarter of 2022.

General and administrative expenses: General and administrative expenses were a gain of $11.1 million (after including a foreign exchange gain of $18.7 million) in the third quarter of 2022, compared to a gain of $6.4 million (after including a foreign exchange gain of $15.2 million) in the second quarter of 2022. Excluding the foreign exchange gain, G&A expenses were $7.6 million in the third quarter of 2022, which were mainly attributable to personnel expenses of $2.8 million, including the share-based payment charge of $0.6 million, insurance costs of $1.5 million, and legal and professional fees of $2.3 million. Excluding the foreign exchange gain, G&A expenses for the second quarter were $8.8 million and were mainly attributable to personnel expenses of $4.3 million, including the share-based payment charge of $2.1 million, insurance costs of $1.6 million, and legal and professional fees of $1.0 million.

·Net Income: For the third quarter of 2022, the Company generated a net income attributable to its shareholders of $8.2 million, or $0.22 both per fully diluted share and per basic share, compared to a net income attributable to shareholders of $15.7 million, or $0.41 per fully diluted share and $0.42 per basic share, for the second quarter of 2022.

Recent Corporate Developments

Clinical developments:

·On October 31, 2022, we announced the dosing of the first patient in HBV003, a phase 2b clinical trial of VTP-300 to evaluate the optimal timing of low dose nivolumab and impact of additional doses of the MVA boost for a sustained decline in HBsAG.

Pre-clinical developments:

·On October 27, 2022, we announced the publication of research from VTP-1100 in Cell that demonstrates anti-tumor activity achieved with intravenous (IV) vaccination of a SNAPvax construct in an animal model. The study demonstrates that IV administration of SNAPvax primes and expands antigen-specific T cells and reverses suppression in the tumor microenvironment, which promotes T cell infiltration and tumor cell killing. An Investigational New Drug (IND) application submission is expected during the first half of 2023 for HPV related cancer.
·On November 7, 2022 Dr. Young-Suk Lim, Professor of Gastroenterology in the Liver Center at University of Ulsan College of Medicine, presented a poster reporting Phase 1b/2a clinical trial data on VTP-300 at AASLD. The poster presentation showed VTP-300 immunotherapy, as monotherapy and when combined with low dose nivolumab at the boosting time point, was immunogenic and showed a sustained reduction in HBsAg in well-controlled CHB patients, and was administered with no treatment related SAEs and infrequent transient transaminitis. Two of five patients dosed in cohort 3 (ChAdOx1-HBV + MVA-HBV with low dose nivolumab given at the boost) with starting HBsAg levels below 100 achieved non-detectable levels of surface antigen at the data cutoff.

Company Leadership:

·On September 20, 2022, we announced the promotion of Gemma Brown to Chief Financial Officer.

Upcoming Milestones

·In addition to the recent developments detailed above, in the fourth quarter of 2022 the Company expects to

§Open a Phase 1/2 clinical trial of VTP-850 in patients with prostate cancer

·In the first quarter of 2023, the Company

§Intends to conduct an interim efficacy review of HPV001, a Phase 1b/2 clinical trial of VTP-200, a potential treatment for low grade HPV-related cervical lesions
§Expects to have FPFV for VTP-850 in our prostate cancer program
§Intends to move its U.S. team into a new, state of the art facility in Germantown, Maryland

·In 2023, the Company expects to

§Submit IND applications for its two lead SNAPvax candidates, VTP-1000 for the treatment of celiac disease and VTP-1100 for the treatment of HPV-associated cancers
§Have FPFV for VTP-1100 in our HPV cancer program
§Have FPFV for VTP-1000 in our Celiac disease program
§Present data from multiple ongoing clinical studies at AASLD and The European Association for the Study of the Liver (EASL) conferences

·Research and development expenses: Research and development expenses were $9.7 million in the third quarter of 2022 compared to $9.7 million in the second quarter of 2022, showing consistent total spend as we continue to advance our pipeline. The quarter on quarter R&D expense per program is outlined in the following table.

On November 10, 2022 Yumanity Therapeutics, Inc. ("Yumanity" or the "Company") (Nasdaq: YMTX) reported that the registration statement on Form S-4 (the "Registration Statement"), relating to the previously announced asset sale to Janssen Pharmaceutica NV ("Janssen") and merger with Kineta, Inc. ("Kineta"), has been declared effective by the U.S. Securities and Exchange Commission (Press release, Kineta, NOV 10, 2022, View Source;utm_medium=rss&utm_campaign=kineta-announces-effectiveness-of-registration-statement-on-form-s-4-in-connection-with-proposed-reverse-merger-with-yumanity-therapeutics-ymtx [SID1234623730]).

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In June 2022, the Company announced definitive agreements for two strategic transactions. The first definitive agreement is an asset purchase agreement for the sale of Yumanity’s lead clinical-stage product candidate, YTX-7739, as well as Yumanity’s unpartnered discovery-stage neuroscience product candidates and targets to Janssen, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, for $26 million in cash. In connection with the closing of the proposed transaction, Yumanity plans to distribute the remaining available cash proceeds from the sale to Yumanity stockholders via a one-time dividend, net of any amounts retained for outstanding obligations and net cash requirements associated with the proposed merger between Yumanity and Kineta. The amount of such dividend will depend on many factors and will not be determined until closer to the closing date.

Under the second definitive agreement, Kineta will become a wholly-owned subsidiary of Yumanity in an all-stock transaction, resulting in a combined publicly traded company re-named Kineta, Inc., that will focus on developing next-generation immunotherapies that address cancer immune resistance and continue Yumanity’s ongoing research collaboration with Merck & Co. in amyotrophic lateral sclerosis and frontotemporal lobar dementia. Upon completion of the proposed merger, on a pro forma basis and based upon the number of Yumanity shares to be issued in the proposed merger, and after giving effect to a concurrent private investment in public equity ("PIPE") led by Growth & Value Development Inc. for an aggregate purchase price of approximately $30.0 million, current Kineta stockholders are expected to own approximately 68.2% of the combined company, current Yumanity stockholders are expected to own approximately 12.0% of the combined company, and the PIPE investors are expected to own approximately 19.8% of the Yumanity common stock. The actual allocation will be subject to adjustment based on each company’s outstanding equity ownership and Yumanity’s net cash balance at the time of the closing of the proposed merger.

Yumanity will mail the definitive proxy statement/prospectus (the "Proxy Statement") to stockholders of record as of the close of business on November 4, 2022. The Proxy Statement contains a notice and will be accompanied by a voting instruction form or a proxy card relating to the special meeting of Yumanity’s stockholders to approve the asset sale and merger (the "Special Meeting") which will be held in a virtual-only format via live audio webcast at 10:00 a.m. Eastern Time, on December 13, 2022, at www.virtualshareholdermeeting.com/YMTX2022SM, unless postponed or adjourned to a later date.

If the proposals at the Special Meeting are approved, the parties anticipate that the asset sale to Janssen and merger with Kineta will close and the combined company will commence trading on Nasdaq under the new ticker symbol "KA" shortly thereafter, subject to the satisfaction or waiver, as applicable, of all other closing conditions.

Every stockholder’s vote is important, regardless of the number of shares held. Accordingly, Yumanity requests that each stockholder complete, sign, date and return a proxy card (online or by mail) as soon as possible to ensure that the stockholder’s shares will be represented at the Special Meeting. Stockholders who hold shares in "street name" (i.e., those stockholders whose shares are held of record by a broker, bank or other nominee) should contact their broker, bank or nominee to ensure that their shares are voted.

If any YMTX stockholder does not receive the Proxy Statement, such stockholder should (i) confirm his or her Proxy Statement’s status with his or her broker or (ii) contact Bob Marese of MacKenzie Partners at [email protected] or John Bryan of MacKenzie Partners at [email protected]. Banks and brokers can place a collect call to Bob Marese at 212-929-5405 or John Bryan at 212-929-5735.

On November 10, 2022 ImmunityBio, Inc. (NASDAQ: IBRX),– NEJM Evidence reported that has published results from the QUILT 3.032 trial studying N-803 plus BCG in adults with NMIBC CIS with or without Ta/T1 papillary disease (Press release, ImmunityBio, NOV 10, 2022, View Source [SID1234623729]). These positive data form the basis of ImmunityBio’s BLA for BCG-unresponsive NMIBC CIS, which the FDA accepted for review in July 2022.

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The published results demonstrate that in patients with BCG-unresponsive NMIBC CIS and papillary disease, BCG plus N-803 (referred to as NAI) CRs were achieved with a persistence of effect with 90% probability of avoiding cystectomies in responders, a life-changing procedure of removing the bladder, and 100% bladder cancer-specific survival at 24 months. This investigational therapy represents an important clinical benefit addressing an unmet need of avoiding a cystectomy in this high-risk bladder cancer population.

"The peer review and publication of data in NEJM Evidence highlights the significance of the positive results of the QUILT 3.032 trial in patients with BCG-unresponsive NMIBC," said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. "We’re targeting the 10th most commonly diagnosed cancer and the one with the highest lifetime treatment costs per patient as a result of the prolonged course of the disease and the need for repeated surgical and treatment intervention. These data further our understanding of N-803’s unique role in potentially boosting the proliferation of natural killer and T cells while synergistically enhancing BCG efficacy."

Patients with intermediate or high-risk NMIBC typically receive a treatment of transurethral resection of the bladder tumor (TURBT) followed by BCG intravesical instillation. However, cancer will recur in 30% to 40% of patients with NMIBC despite adequate treatment with BCG. Moreover, even among those in whom a complete response is achieved with BCG, up to 50% see their cancer return.

Treatment options for BCG-unresponsive NMIBC patients are limited. Pembrolizumab was approved by the FDA for this indication in 2020, based on findings from the KEYNOTE-057 study in which the CR rate in NMIBC CIS patients was 41% with a median response duration of 16.2 months. The combination of N-803 plus BCG produced both a higher CR rate and more durable responses.

In patients who received intravesical N-803 plus BCG (cohort A), a CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months 95% CI 59.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan–Meier–estimated probability of avoiding cystectomy and of disease-specific survival was 89.2% and 100%, respectively.

In patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received N-803 plus BCG (cohort B), the Kaplan–Meier–estimated disease-free survival (DFS) rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]).

Most adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%) and comparable to adverse events associated with BCG alone.

About the QUILT 3.032 Trial

In this phase 2/3, open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical N-803 plus BCG (cohort A) or N-803 alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received N-803 plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival, and overall survival were secondary end points for cohort A.

The results of this phase 2/3 study are currently being reviewed by the FDA, and a decision from the FDA regarding approval for use of the biologics N-803 plus BCG in adults with BCG-unresponsive NMIBC CIS is expected on May 23, 2023.

ImmunityBio’s IL-15 superagonist 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 (generic name nogapendekin alfa inbakicept or NAI) 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.

N-803 has been studied in more than 700 patients in multiple phase 1 and 2 trials in both liquid and solid tumors. In addition to the study in NMIBC, it is currently being studied in trials for pancreatic cancer, non-small-cell lung cancer, non-Hodgkin’s lymphoma, and HIV.

N-803 has received both Breakthrough Therapy and Fast Track designations by the FDA for the treatment of BCG-unresponsive NMIBC CIS, as well as Fast Track designation for BCG-unresponsive NMIBC papillary and BCG-naïve NMIBC CIS. However, it is important to note such designations may not lead to a faster development process or regulatory review and may not increase the likelihood that a product candidate will receive approval. Seminal patents covering intravesical administration of BCG and N-803 were issued (US 11,173,191 B2 and US 9,925,247 B2) providing term coverage until 2035.