A Phase II Study of N-803 Alone or in Combination With BN-Brachyury Vaccine or Bintrafusp Alfa (M7824) for Participants With Castration Resistant Prostate Cancer

Background:
Prostate cancer does not trigger a strong immune response in the body. Hormone therapy, to reduce levels of testosterone in the body, can be helpful to treat some prostate cancers. However, castration-resistant prostate cancer (CRPC) keeps growing even when the testosterone is reduced to a very low level. Men with metastatic CRPC survive an average of only 3 years. More effective treatments are needed.
Objective:
To test whether an immunotherapy drug (N-803), alone or in combination with other drugs, can help treat CRPC.
Eligibility:
Males aged 18 or older with CRPC. Prior treatment with testosterone-lowering therapy is required.
Design:
Participants will be screened. They will have blood and urine tests. They will have a CT scan of the chest, abdomen, and pelvis.
They will continue to receive hormone therapy for prostate cancer.
Participants will come to the NIH clinic once a week for the first 4 weeks. Then they will come once every 2 weeks. Visits will last up to 8 hours. The study will continue up to 3 years.
All participants will receive N-803 once every 2 weeks. The drug is injected just under the skin with a small needle.
Some participants will receive N-803 plus another drug (brachyury vaccine). This drug is also injected under the skin with a small needle.
Some participants will receive N-803 plus a different drug (bintrafusp alfa) once every 2 weeks. This drug is given through a tube attached to a needle placed in a vein in the arm.
Some participants may receive all 3 drugs.
Participants will have imaging scans every 12 weeks.

Start Date01 Apr 2024

Sponsor / Collaborator

National Cancer Institute

CTR20220946 / RecruitingPhase 3

一项在多项Bintrafusp alfa（M7824）临床研究中收集受试者长期数据的开放性、多中心随访研究

[Translation] An open-label, multicenter follow-up study to collect long-term data from subjects in multiple Bintrafusp alfa (M7824) clinical studies

1. 旨在评价Bintrafusp alfa在完成母研究的初步/主要分析后继续接受治疗的实体瘤受试者中的临床安全性； 2. 旨在基于OS评价Bintrafusp alfa的临床疗效； 3. 旨在基于PFS评价Bintrafusp alfa的临床疗效； 4. 旨在基于DOR评价Bintrafusp alfa的临床疗效。

[Translation]

1. To evaluate the clinical safety of Bintrafusp alfa in subjects with solid tumors who continued to receive treatment after completing the primary/primary analysis of the parent study; 2. To evaluate the clinical efficacy of Bintrafusp alfa based on OS; 3. To evaluate the clinical efficacy of Bintrafusp alfa based on PFS; 4. To evaluate the clinical efficacy of Bintrafusp alfa based on DOR.

Start Date30 Sep 2022

Sponsor / Collaborator

Merck Healthcare KGaA

[+3]

NCT05012098 / CompletedPhase 2IIT

Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON).

Background:
Olfactory neuroblastoma (ONB) is a rare cancer of the nasal cavity. At diagnosis, it is usually locally advanced. It tends to spread to the neck. Sometimes it spreads to the lungs and bones. Researchers want to find a better way to treat it.
Objective:
To learn if giving immunotherapy drug bintrafusp alfa can help ONB shrink or disappear.
Eligibility:
People aged 18 years and older diagnosed with recurrent or metastatic ONB that has not responded to standard treatment.
Design:
Participants will be screened with a medical history, blood and urine tests, and physical exam. Their ability to perform their normal activities will be assessed. They will have an electrocardiogram to evaluate their heart. They will have imaging scans and/or a nuclear bone scan, as needed. For some scans, they may receive a contrast dye.
Some screening tests will be repeated during the study.
Participants will receive bintrafusp alfa once every 2 weeks for 26 doses. They will get it intravenously over 60 minutes. They may get other medicines to prevent side effects. They will complete health questionnaires. Visits will last 4-6 hours.
Participants may have optional tumor biopsies.
Participants will have an end of treatment visit within 7 days after they stop taking the study drug. About 28 days after treatment ends, they will have a safety visit. They will have follow-up visits every 3 months for the first year, then every 6 months for years 2-5, and then once a year after that for the rest of their life. If their disease progresses, they may be eligible for re-treatment with the study drug

Start Date21 Jun 2022

Sponsor / Collaborator

National Cancer Institute

100 Clinical Results associated with Bintrafusp alfa

100 Translational Medicine associated with Bintrafusp alfa

100 Patents (Medical) associated with Bintrafusp alfa

Literatures (Medical) associated with Bintrafusp alfa

04 Nov 2024·MOLECULAR CANCER THERAPEUTICS

Dual A2A/A2B Adenosine Receptor Antagonist M1069 Counteracts Immunosuppressive Mechanisms of Adenosine and Reduces Tumor Growth In Vivo

Article

Author: Matevossian, Armine ; Boesler, Carsten ; Belousova, Natalya ; Huck, Bayard ; Schiemann, Kai ; Kradjian, Giorgio ; Petrova, Elissaveta ; Pandya, Meghana ; Schann, Stephan ; Kitzing, Thomas ; Nallaparaju, Kalyan C. ; Zaynagetdinov, Rinat ; Wagner, Christian ; Krauel, Eva-Maria ; Chen, Zhouxiang ; Aral, Esengul ; Lecomte, Marc ; Moisan, Jacques ; Blayo, Anne Laure

Abstract:

While A2A adenosine receptor (AR) was considered as a major contributor to adenosine-mediated immunosuppression, A2B, having the lowest affinity to adenosine, has also emerged as a potential contributor to tumor promotion. Therefore, in adenosine-rich tumor microenvironment (TME), where A2B could be complementary and/or compensatory to A2A, simultaneous targeting of A2A and A2B ARs can provide higher potential for cancer immunotherapy. We developed M1069—a highly selective dual antagonist of the A2A and A2B AR. In assays with primary human and murine immune cells, M1069 rescued IL2 production from T cells (A2A dependent) and inhibited VEGF production by myeloid cells (A2B dependent) in adenosine-high settings. M1069 also demonstrated superior suppression of the secretion of protumorigenic cytokines CXCL1, CXCL5, and rescue of IL12 secretion from adenosine-differentiated dendritic cells compared to an A2A-selective antagonist (A2Ai). In a one-way mixed lymphocyte reaction (MLR) assay, adenosine-differentiated human and murine dendritic cells treated with M1069 demonstrated superior T-cell stimulatory activity compared to dendritic cells differentiated in presence of A2Ai. In vivo, M1069 decreased tumor growth as a monotherapy and enhanced antitumor activity of bintrafusp alfa (BA) or cisplatin in syngeneic adenosinehi/CD73hi 4T1 breast tumor model, but not in the CD73 knockout 4T1 tumor model or in adenosinelow/CD73low MC38 murine colon carcinoma model. In summary, our dual A2A/A2B AR antagonist M1069 may counteract immune-suppressive mechanisms of high concentrations of adenosine in vitro and in vivo and enhance the antitumor activity of other agents, including BA and cisplatin.

29 Jun 2024·British journal of cancer

Blockade of TGF-β and PD-L1 by bintrafusp alfa promotes survival in preclinical ovarian cancer models by promoting T effector and NK cell responses

Article

Author: Greer, Peter A ; Kment, Jacob ; Young, Stephanie ; Newsted, Daniel ; Vermeulen, Michael C ; Laight, Brian J ; Lan, Yan ; Craig, Andrew W

Abstract:

Background:

Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels of transforming growth factor-β (TGF-β) in ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade of TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour immune responses in preclinical HGSC models.

Methods:

BA is a first-in-class bifunctional inhibitor of TGF-β and PD-L1, and was tested for effects on overall survival and altered TIME in syngeneic HGSC models.

Results:

Using a mouse ID8-derived HGSC syngeneic model with IFNγ-inducible PD-L1 expression, BA treatments significantly reduced ascites development and tumour burden. BA treatments depleted TGF-β and VEGF in ascites, and skewed the TIME towards cytotoxicity compared to control. In the BR5 HGSC syngeneic model, BA treatments increased tumour-infiltrating CD8 T cells with effector memory and cytotoxic markers, as well as cytolytic NK cells. Extended BA treatments in the BR5 model produced ∼50% BA-cured mice that were protected from re-challenge. These BA-cured mice had increased peritoneal T-effector memory and NK cells compared to controls.

Conclusions:

Our preclinical studies of BA in advanced ovarian cancer models support further testing of BA as an improved immunotherapy option for patients with advanced ovarian cancer.

21 May 2024·Clinical and experimental dermatology

Bintrafusp alfa induced multiple self-healing cutaneous keratoacanthoma-like squamous proliferations

Article

Author: Waters, Margo ; Subhadarshani, Sweta ; Shaughnessy, Cristin Nealon

We present a case where bintrafusp alfa induced self-resolving keratoacanthomas and squamous cell carcinoma (SCC)-like cutaneous proliferations in a patient. With the development and use of novel targeted therapies, it is important to be aware of possible cutaneous adverse events. It is also prudent to emphasize that in many cases the development of lesions such as SCC-like cutaneous proliferations is reversible, which should be considered when counselling patients on whether to stop treatment.

News (Medical) associated with Bintrafusp alfa

13 Sep 2024

·medcitynews.com

3 Biotech IPOs, $703M Raised for Clinical Trials in Cancer, Immunology & Endocrine Disorders - MedCity News

Cancers of the head and neck can be treated with several drugs on the market, but for certain patients diagnosed with this this common type of cancer, outcomes are worse and better therapeutic options are needed. Bicara Therapeutics is developing a therapy that could provide a treatment alternative and the company now has $315 million in IPO cash to finance a pivotal study. Boston-based Bicara was able to raise more than it planned. In preliminary IPO terms set on Monday, the company aimed to offer 11.7 million shares priced in the range of $16 to $18 each. On Wednesday, Bicara increased the proposed stock sale to 14.7 million shares offered in the same targeted price range. When shares finally priced late Thursday, Bicara boosted the deal size yet again, offering 17.5 million shares for $18 each, right at the top of the targeted price range. Those shares now trade on the Nasdaq under the stock symbol “BCAX.” Most head and neck squamous cell carcinoma (HNSCC) cases come from exposure to carcinogens such as tobacco smoke or from human papillomavirus (HPV), Bicara says in its IPO filing. That virus can lead to cellular changes that over time, become precancerous and then cancerous. However, an estimated 80% of recurrent or metastatic HNSCC cases are HPV-negative. These tumors are associated with an increased risk of fatal tumor bleeding, excruciating pain, and difficulty swallowing. Sponsored Post What Healthcare Can Learn from Costco The path forward is clear: employers must evaluate their health plan the same way they do their Saturday shopping excursion. By Jeff Bak, Imagine360 CEO and President Bicara’s drugs are antibodies engineered to address solid tumors by hitting two validated cancer targets. The company’s lead program, ficerafusp alfa, is a bifunctional antibody drug designed to bind to epidermal growth factor receptor (EGFR) and human transforming growth factor beta (TGF-beta). TGF-beta is an important target because high signaling from this protein is associated with resistance to the class of immunotherapies called checkpoint inhibitors. For that reason, drugs that hit this target have been tested as a way to potentially overcome this resistance. GSK and Merck KGaA tried this approach with a bifunctional protein, bintrafusp alfa. But clinical trial results showed the experimental therapy fell short on measures of efficacy. In its IPO filing, Bicara said such failures may be due to insufficient anti-tumor activity, possibly because the immunotherapy is being expressed in immune tissue rather than the tumor microenvironment (TME) where it’s needed. Bicara says the dual approach of its drug blocks survival signaling from EGFR as well as immunosuppressive TGF-beta signaling in the TME. Bicara has been testing its experimental drug in combination with the blockbuster Merck immunotherapy pembrolizumab, brand name Keytruda, whose approved indications include HNSCC. An ongoing Phase 1/1b study of the Bicara drug includes a group of HNSCC patients who had not previously received treatment after their cancer had advanced. In this cohort, Bicara said the combination of the study drug and Keytruda led to a 54% overall response rate in patients who could be evaluated for efficacy. In patients whose disease was HPV negative, the overall response rate was 64%. For context, the historical response rate in a Phase 3 test of Keytruda monotherapy in HNSCC was 19%, the company said in the filing. The company expects to report more Phase 1/1b data at a medical meeting in 2025. “Based on the clinical data generated to date, we believe that ficerafusp alfa in combination with pembrolizumab has the potential to become a first-line standard of care therapy in HPV-negative [recurrent/metastatic] HNSCC,” Bicara said in the filing. “We also believe ficerafusp alfa has the potential to provide meaningful clinical benefit in other solid tumors where there is a strong biologic rationale for the dual inhibition of both EGFR and TGF-beta, such as colorectal cancer and other squamous cell carcinomas which typically overexpress EGFR and TGF-beta pathways.” presented by Sponsored Post The Promise of Value-Based Care and MedTech Innovation Monica Vajani, Executive Director for mHUB’s MedTech Accelerator, discusses how mHUB is helping innovators transition healthcare towards value-based care. By Monica Vajani - mHUB A pivotal Phase 2/3 clinical trial is planned that will test the Bicara therapy in combination with the Merck immunotherapy pembrolizumab, brand name Keytruda, as a first-line treatment for advanced HNSCC. Bicara expects this study will start by the end of this year or in the first quarter of 2025. Bicara formed in 2018. The following year, the company licensed certain fusion proteins from Biocon Limited. The most advanced of those fusion proteins was ficerasfusp alfa. There are no future milestone payments or royalties tied to the deal, Bicara said in the filing. The prospectus says Bicara has raised $353.1 million since its inception. The most recent financing was a $165 million Series C round announced last December. Biocon is Bicara’s largest shareholder, owning an 11.28% post-IPO stake, according to the filing. RA Capital Management owns a 10.5% stake after the IPO. As of the end of the second quarter of this year, Bicara reported a cash position of $203.9 million. Combined with the IPO proceeds, the company plans to spend about $265 million on the development of ficerafusp alfa in HNSCC, including the pivotal study and the filing of a biologics license application. Another $30 million is earmarked for the expansion of its lead drug candidate in additional HNSCC patient groups. And $25 million is set aside for advancing clinical development of the drug in additional types of solid tumors, such as colorectal cancer and other squamous cell carcinomas. Zenas’s IPO Pulls in $225M for Pipeline in a Product Opportunity in I&I Zenas Biopharma, a company developing antibody drugs to treat immunology and inflammation (I&I) disorders, raised $225 million. The company late Thursday priced more than 13.23 million shares at $17 each. When Zenas set preliminary financial terms this week, it aimed to offer 11.76 million shares in the range of $16 to $18 apiece, which would have raised $199.9 million at the pricing midpoint. Zenas’s shares will trade on the Nasdaq under the stock symbol “ZBIO.” Excessive activity of B cells, a type of immune cell, is associated with a range of autoimmune disorders. While antibody drugs are currently available that treat these conditions by depleting B cells, Zenas contends they don’t fully affect B cells in relevant tissue and the dosing regimen of these therapies can be improved. Another concern is that antibody drugs that target and block the proteins CD19 and CD20 on B cells may deplete these cells for six months or longer, which raises the risk of infection and could reduce a patient’s ability to respond to and benefit from vaccines. Zenas’s lead drug candidate is obexelimab, a bifunctional antibody designed to bind to CD19 and Fc gamma receptor IIb, both targets that are broadly expressed on B cells. According to Zenas, this approach mimics a natural antigen-antibody complex for inhibiting B cells. This mechanism of action is intended to inhibit the activity of B cells without completely depleting them. Zenas acquired global rights to obexelimab from Xencor in 2021. The company had previously licensed other programs from Xencor; those programs are still preclinical. While Zenas believes obexelimab has broad potential in I&I, the company is initially focusing on four indications: immunoglobulin G4-related disease (IgG4-RD), multiple sclerosis, systemic lupus erythematosus, and warm autoimmune hemolytic anemia (wAIHA). Zenas’s drug is furthest along in IgG4-RD, a chronic inflammatory condition that affects multiple organs. Standard of care includes corticosteroids. Roche’s CD20-targeting antibody drug, Rituxan, can also be used to treat the condition. Zenas is continuing a Phase 3 test of its lead drug in IgG4-RD. Since inception, Zenas said it had raised $358.3 million from investors. The company’s most recent financing was a $200 million Series C round in May led by SR One. That investor owns a 7% post-IPO stake in Zenas, according to the filing. Xencor is Zenas’s largest shareholder with an 8.1% post-IPO stake. As of the end of June, Zenas reported having $183.9 million in cash. That capital, along with the IPO proceeds, will broadly support the advancement of obexelimab. Zenas plans to spend about $100 million on clinical development of the drug, including the completion of a Phase 3 study in patients with IgG4-RD. This drug candidate will also be evaluated in separate Phase 2 tests in multiple sclerosis, lupus, and wAIHA. The company expects its capital will last for the next two years. MBX Bio’s Longer-Acting Peptide Drugs Land $163M for Clinical Trials MBX Biosciences’ IPO raised $163 million for a pipeline that includes a lead program in the clinic for a rare hormone deficiency with few FDA-approved treatments. Carmel, Indiana-based MBX priced its offering of 10.2 million shares at $16 each, which was the top of $14 to $16 per share price range it set earlier this week. The company was able to boost the deal size, offering 1.7 million more shares than it had initially planned. MBX’s shares will trade on the Nasdaq under the stock symbol “MBX.” MBX’s drugs come from a platform technology that engineering peptides with a longer duration of action that enables less frequent dosing intervals. This technology is based on research from Indiana University. Lead program MBX 2109 is a potential treatment for chronic hypoparathyroidism, a condition in which the parathyroid glands do not produce enough parathyroid hormone to regulate levels of calcium and phosphate in the blood. The first FDA-approved therapy for this condition is Takeda Pharmaceutical’s Natpara, an engineered version of the hormone. But Takeda has said it will stop offering Natpara due to ongoing manufacturing problems. Patients have a new alternative following FDA approval last month of Ascendis Pharma’s Yorvipath, a peptide injected once-daily to bring parathyroid hormone levels within the normal range. With MBX 2109, MBX aims to offer chronic hypoparathyroidism patients less burdensome once-weekly dosing. In Phase 1 testing, the company reported its engineered peptide achieved parathyroid hormone levels comparable to those achieved by a continuous infusion. A Phase 2 study dosed its first patient last month; preliminary data are expected in the third quarter of next year. Another engineered peptide, MBX 1416, in Phase 1 development for post-bariatric hypoglycemia (PBH). In this rare condition, bariatric surgery patients go on to develop dangerously low blood sugar levels. There are no FDA-approved therapies for this rare condition, but MBX isn’t alone in the pursuit for one. Amylyx Pharmaceuticals picked up its Phase 3-ready PBH peptide drug from the bankruptcy auction of Eiger BioPharmaceuticals. Another engineered peptide, MBX 4291, is in preclinical development for obesity. According to the IPO filing, MBX’s cash position at the end of June was $55.3 million. That capital, along with the IPO proceeds, will support clinical trials. MBX plans to spend $148.6 million to take its lead program through mid-stage development and into Phase 3 testing in chronic hypoparathyroidism and to advance its PBH drug through Phase 1 and Phase 2 testing. Another $31.2 million is set aside to advance the obesity program into the clinic.

ImmunotherapyPhase 1Phase 2Phase 3Clinical Result

01 Aug 2024

·www.globenewswire.com

PDS Biotech Aligns with FDA on Phase 3 Trial in HPV16-Positive First-Line Recurrent or Metastatic Head and Neck Cancer

Company to initiate Phase 3 VERSATILE-003 trial in Q4 2024 Conference Call Today at 8:00 a.m. Eastern Time PRINCETON, N.J., Aug. 01, 2024 (GLOBE NEWSWIRE) -- PDS Biotechnology Corporation (Nasdaq: PDSB) (“PDS Biotech” or the “Company”), a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers and the development of infectious disease vaccines, today announced that it has received the official minutes from its meeting with the U.S. Food and Drug Administration (“FDA”) regarding next steps in its planned Phase 3 clinical trial of its Versamune® based investigational immunotherapy designed to stimulate a targeted T cell attack against HPV16-positive head and neck squamous cell carcinoma (“HNSCC”). The Company will host a conference call today at 8:00 a.m. ET to discuss details of the anticipated Phase 3 clinical trial of Versamune® HPV (formerly PDS0101) in this indication. PDS Biotech presented the FDA with recent data from both the VERSATILE-002 study of Versamune® HPV + pembrolizumab, and the triple combination of Versamune® HPV + PDS01ADC + bintrafusp alfa. The Company also provided an updated design of the Phase 3 VERSATILE-003 trial of Versamune® HPV + pembrolizumab which included updated statistical endpoints based on recent and more mature survival data. PDS Biotech proposed the addition of a third arm to the study which would be a triple combination of Versamune® HPV + PDS01ADC + pembrolizumab. The first part of the study would therefore involve a dose optimization of PDS01ADC in the novel combination. The FDA supported the strategy and development of the double and triple combinations. Also, the FDA requested additional safety analysis in the lead-in PDS01ADC dose optimization part of the study. To avoid potential delays in initiating the randomized trial, the FDA agreed that the dose optimization should be done separately and the registrational trial of the revised 2-arm double combination trial, VERSATILE-003, should proceed. The Versamune® HPV + pembrolizumab combination has received Fast Track designation. “We appreciate the FDA’s support in the development of both the double and triple Versamune® HPV-based combinations. We are also pleased to have aligned on initiating the updated VERSATILE-003 study,” said Frank Bedu-Addo, PhD, President and Chief Executive Officer of PDS Biotech. “The VERSATILE-002 results have matured significantly and positively over the last year, allowing us to revise the statistical endpoints of the study to provide additional robustness to the study design. We continue to believe that the combination, based on encouraging survival, disease control response rates and safety has the potential to significantly advance the treatment of HPV16-positive HNSCC. Our goal now is to investigate Versamune® HPV + pembrolizumab’s potential as the first targeted immunotherapy for HPV16-positive HNSCC. The addition of PDS01ADC in the future has the potential to provide further clinical benefit to an effective targeted immunotherapy.” Kirk Shepard, MD, Chief Medical Officer, continued, “We have contracted with a clinical research organization and the preparatory work is advancing to begin enrollment in the VERSATILE-003 Phase 3 clinical trial in first-line treatment of patients with recurrent or metastatic HPV16-positive HNSCC, with overall survival as the study’s primary endpoint. Our VERSATILE-003 trial has significant key opinion leader support, including from the investigators involved in VERSATILE-002, and we have lined up a significant number of the target sites that have indicated strong interest in participating in the trial.” Conference Call DetailsDate: August 1, 2024Time: 8:00 a.m. ET Dial-in: 1-877-704-4453 or 1-201-389-0920 Webcast Registration: Click HereCall MeTM Registration: Click Here (Available 15 minutes prior to call) About PDS Biotechnology PDS Biotechnology is a late-stage immunotherapy company focused on transforming how the immune system targets and kills cancers and the development of infectious disease vaccines. The Company plans to initiate a pivotal clinical trial in 2024 to advance its lead program in advanced HPV16-positive head and neck squamous cell cancers. PDS Biotech’s lead investigational targeted immunotherapy Versamune® HPV is being developed in combination with a standard-of-care immune checkpoint inhibitor, and also in a triple combination including PDS01ADC, an IL-12 fused antibody drug conjugate (ADC), and a standard-of-care immune checkpoint inhibitor. For more information, please visit www.pdsbiotech.com. Forward Looking Statements This communication contains forward-looking statements (including within the meaning of Section 21E of the United States Securities Exchange Act of 1934, as amended, and Section 27A of the United States Securities Act of 1933, as amended) concerning PDS Biotechnology Corporation (the “Company”) and other matters. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the Company’s management, as well as assumptions made by, and information currently available to, management. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” “forecast,” “guidance”, “outlook” and other similar expressions among others. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the Company’s ability to protect its intellectual property rights; the Company’s anticipated capital requirements, including the Company’s anticipated cash runway and the Company’s current expectations regarding its plans for future equity financings; the Company’s dependence on additional financing to fund its operations and complete the development and commercialization of its product candidates, and the risks that raising such additional capital may restrict the Company’s operations or require the Company to relinquish rights to the Company’s technologies or product candidates; the Company’s limited operating history in the Company’s current line of business, which makes it difficult to evaluate the Company’s prospects, the Company’s business plan or the likelihood of the Company’s successful implementation of such business plan; the timing for the Company or its partners to initiate the planned clinical trials for PDS01ADC, PDS0101, PDS0203 and other Versamune® and Infectimune® based product candidates; the future success of such trials; the successful implementation of the Company’s research and development programs and collaborations, including any collaboration studies concerning PDS01ADC, PDS0101, PDS0203 and other Versamune® and Infectimune® based product candidates and the Company’s interpretation of the results and findings of such programs and collaborations and whether such results are sufficient to support the future success of the Company’s product candidates; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund its disclosed clinical trials, which assumes no material changes to the Company’s currently projected expenses), futility analyses, presentations at conferences and data reported in an abstract, and receipt of interim or preliminary results (including, without limitation, any preclinical results or data), which are not necessarily indicative of the final results of the Company’s ongoing clinical trials; any Company statements about its understanding of product candidates mechanisms of action and interpretation of preclinical and early clinical results from its clinical development programs and any collaboration studies; the Company’s ability to continue as a going concern; and other factors, including legislative, regulatory, political and economic developments not within the Company’s control. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the other risks, uncertainties, and other factors described under “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in the documents we file with the U.S. Securities and Exchange Commission. The forward-looking statements are made only as of the date of this press release and, except as required by applicable law, the Company undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. Versamune® and Infectimune® are registered trademarks of PDS Biotechnology Corporation. Investor Contact:Mike MoyerLifeSci AdvisorsPhone +1 (617) 308-4306 Email: mmoyer@lifesciadvisors.com Media Contact:Gina Mangiaracina6 DegreesPhone +1 (917) 797-7904Email: gmangiaracina@6degreespr.com

ImmunotherapyPhase 3Fast Track

13 Feb 2024

·www.fiercebiotech.com

Japan's Ono Pharma taps Texas startup Shattuck for $227M bifunctional fusion protein deal

Ono will select a pair of targets from Shattuck’s portfolio of bifunctional fusion proteins. Shattuck Labs’ pipeline of bifunctional fusion proteins has caught the attention of Ono Pharmaceutical, with the Japanese drug developer penning a $227 million biobucks deal focused on autoimmune and inflammatory diseases. Under the agreement, Ono will select a pair of targets from Shattuck’s portfolio with an exclusive option to develop and commercialize “multiple products.” In return, Texas-based Shattuck will receive an undisclosed upfront payment and be in line for licensing, regulatory and commercial milestones which could add up to $227 million in total, along with tiered royalties on any approved products. “We have prioritized autoimmune and inflammatory diseases for a select group of preclinical pipeline candidates as we continue to expand into areas of high unmet need,” Shattuck’s CEO Taylor Schreiber, M.D., Ph.D., explained in the release. “This collaboration aligns with our strategy to unlock further value from our bifunctional fusion protein platform and scientific expertise.” Bifunctional proteins have attracted Big Pharma interest in the past, with GSK and Merck KGaA partnering up to work on bintrafusp alfa in 2019. Those efforts, designed to combine a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein, ended in a high-profile failure two years later and the collaboration was dissolved in the wake of a series of clinical setbacks. Still, Ono—which co-developed Bristol Myers Squibb’s blockbuster PD-1 drug Opdivo—appears to see potential in the modality. Toichi Takino, senior executive officer for discovery and research at the company, expressed admiration for Shattuck’s “generation of functional biologics against therapeutic targets that have been difficult through conventional technologies.” “We hope to add bifunctional fusion proteins discovered and developed by Shattuck into our portfolio to bring innovative drugs for patients suffering from autoimmune and inflammatory diseases as soon as possible,” Takino added.

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100 Deals associated with Bintrafusp alfa

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lung Cancer	Phase 3	RU	Merck KGaA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	US	Merck Serono SpA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	US	Merck Healthcare KGaA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	JP	Merck Serono SpA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	JP	Merck Healthcare KGaA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	AR	Merck Healthcare KGaA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	AR	Merck Serono SpA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	AU	Merck Healthcare KGaA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	AU	Merck Serono SpA	01 Dec 2021
Non-Small Cell Lung Cancer	Phase 3	BE	Merck Healthcare KGaA	01 Dec 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03436563 (CTgov)	Phase 1/2	Adenocarcinoma of large intestine \| Rectal Adenocarcinoma \| Colonic Cancer ... View more	4	Bintrafusp Alfa	wxgfeuvomw(bqfkgqgpmn) = ssfunvkmen czxgxmabgc (zjxtgvcrpn, xapluxqxzd - kuswlnliav) View more	-	27 Nov 2024
NCT02699515 (CTgov)	Phase 1	Locally Advanced Malignant Solid Neoplasm	114	M7824 (Dose Escalation Cohort: M7824 (3 mg/kg))	jwutcdpjqw(flnhftuhez) = xkokzyhrbv jycqfrpsfp (slybatmfut, sgqpbsjzts - bbznqtclkw) View more	-	18 Nov 2024
				M7824 (Dose Escalation Cohort: M7824 (10 mg/kg))	jwutcdpjqw(flnhftuhez) = fujvavjscq jycqfrpsfp (slybatmfut, rxkjaopmrr - mguzzzxrfv) View more
NCT04246489 (Pubmed) Manual	Phase 2	Uterine Cervical Cancer platinum-based chemotherapy	146	Bintrafusp alfa	oxzacoazmy(llzbnruypc) = nzwaskqwxt dgzzfrvgpl (hilsqchkza ) Met View more	Positive	25 Jul 2024
NCT04220775 (CTgov)	Phase 1/2	Recurrent Squamous Cell Carcinoma of the Head and Neck	3	SBRT (Phase 1 Bintrafusp Alfa + SBRT)	pvvpgrmbdk(gibsrjnnxd) = awwmjpedtl ddyhgocgcm (pcjkwjdyxg, mznugrbjoa - ualjksgsmw) View more	-	23 Jul 2024
				SBRT (Phase 2 Bintrafusp Alfa + SBRT)	pvvpgrmbdk(gibsrjnnxd) = iyxudkadbc ddyhgocgcm (pcjkwjdyxg, jpualncorl - mriujtgebg) View more
NCT05005429 (BIMES, ASCO2024)	Phase 2	Malignant Pleural Mesothelioma	47	Bintrafusp alfa 1200mg/m2	xzamdtfvdx(izxvdubknf) = wpuikrwrde fcdvrioeal (mwbcmujrbm, 1.7 - 5.4) View more	Negative	24 May 2024
NCT04349280 (CTgov)	Phase 1	Locally Advanced Urothelial Carcinoma	25	Bintrafusp Alfa (Main Study - Bintrafusp Alfa)	vypdbpgtmf(xvmthynhyu) = qsbimqahhp ejxbphcqot (arlcemuolp, hhktvseove - dajeatmhdg) View more	-	18 Apr 2024
				Bintrafusp Alfa (PACT Phase - Bintrafusp Alfa)	shsgsitmqt(cnjmvpocir) = epwtgmrxei kkdktizevt (mhjdlikdbz, tfmvxkteot - rinuduasvw) View more
NCT04551950 (CTgov)	Phase 1	Locally Advanced Cervical Carcinoma	25	Bevacizumab+Carboplatin+Paclitaxel+Bintrafusp Alfa+Cisplatin (Cohort 1A: Bintrafusp Alfa +Cisplatin/Carboplatin+Paclitaxel+Bevacizumab)	zpnkjbzjta(xjmfaritma) = dfahmwgdjr xsgbmzazum (olhydtcgdc, cinlmiaqak - eibocjxolg) View more	-	08 Mar 2024
				Carboplatin+Paclitaxel+Bintrafusp Alfa+Cisplatin (Cohort1B: Bintrafusp Alfa +Cisplatin or Carboplatin+Paclitaxel)	zpnkjbzjta(xjmfaritma) = fkmsvyalao xsgbmzazum (olhydtcgdc, lweolwdagv - noniuyaziu) View more
NCT03840902 (CTgov)	Phase 2	Non-small cell lung cancer stage III	153	Intensity Modulated Radiation Therapy (IMRT)+Etoposide+Carboplatin+Paclitaxel+M7824+cisplatin+pemetrexed (cCRT Plus M7824 Followed by M7824)	kabbhoemka(aetatcrulu) = zzmrykeiqi giptqdtlvs (jguwyvzkvk, dntydgxpwy - ahhpmxgpxg) View more	-	16 Jan 2024
				Placebo+Etoposide+Carboplatin+Paclitaxel+cisplatin+Durvalumab+pemetrexed (cCRT Plus Placebo Followed by Durvalumab)	kabbhoemka(aetatcrulu) = ddyyvzwnih giptqdtlvs (jguwyvzkvk, evknbvukop - bhbuvzbvuz) View more
NCT03631706 (phase 3, Pubmed \| J Thorac Oncol)	Phase 3	Advanced Lung Non-Small Cell Carcinoma First line PD-L1-high	304	Bintrafusp alfa	dpobvkoawk(wicpizjlkj) = 42.4% vs 13.2% of patients wwgiwunkma (jlgnzewngv )	Negative	01 Dec 2023
				Pembrolizumab
NCT04491955 (CTgov)	Phase 2	Colorectal Cancer \| Small intestine carcinoma	32	NHS-IL12 (M9241) (Cohort 1, Arm 1 Triple Therapy Without NHS-IL12 (M9241))	xwyaunkhkn(rtmghvxnzl) = scnarsqark pyvxwpicoz (kdtvalkstx, blkzalsdrc - cuffhnpnfr) View more	-	14 Nov 2023
				Fowlpox (FPV)-CV301+N-803+modified vaccinia Ankara (MVA)-BN-CV301+M7824+NHS-IL12 (M9241) (Cohort 2, Arm 2a Dose Level (DL) 1, Quad Therapy Dose Escalation)	frnwpkkjjr(dwiwkmojyf) = aaqhlpypla ncijdqfqga (echtzjdbzu, qtroxgzbgv - zcanwzqmfp) View more

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