On May 31, 2023 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported that the US Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application to initiate a Phase 2 study of the first-in-class PRGN-2009 Off-the-Shelf (OTS) AdenoVerse immunotherapy in combination with pembrolizumab in patients with recurrent or metastatic cervical cancer (Press release, Precigen, MAY 31, 2023, View Source [SID1234632302]). The Phase 2 randomized, open-label, two-arm, multicenter study will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab versus pembrolizumab monotherapy in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant. The study will enroll approximately 46 patients who previously have been treated with pembrolizumab for recurrent or metastatic disease.

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In the Phase 1 study, PRGN-2009 was evaluated as a monotherapy (N=6) and in combination with a checkpoint inhibitor (N=11) in patients with recurrent or metastatic human papillomavirus (HPV)-associated cancers. Interim Phase 1 data showed a favorable safety profile of repeated PRGN-2009 administrations in both the monotherapy and the combination arms with no dose limiting toxicities (DLTs). Interim Phase 1 data showed encouraging clinical activity with objective responses when combined with a checkpoint inhibitor in heavily pre-treated recurrent/metastatic cancer patients who had previously failed checkpoint inhibitor treatment. Full Phase 1 data will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 3, 2023 from 8:00 to 11:00 AM CT (Abstract # 2628).

"Cervical cancer is a devastating disease for which there remains a significant unmet need for new and improved treatment options in the recurrent or metastatic setting," said Helen Sabzevari, PhD, President and CEO of Precigen. "We are encouraged by the 30% ORR in the Phase 1 study which demonstrated a favorable safety profile with no dose-limiting toxicities, strong antigen-specific immune response and lack of significant neutralizing antibody response upon repeat administrations in combination with a checkpoint inhibitor. Based on these Phase 1 safety and efficacy data, the FDA has allowed us to treat patients as early as the second line in the recurrent or metastatic setting in this Phase 2 cervical cancer study. Additionally, we are pleased that in collaboration with FDA, we have agreed upon a CMC path to support the delivery of product for the Phase 2 study as well as a future framework to support potential pivotal trials."

Patients in the Phase 2 study will be randomized 1:1 to the combination of PRGN-2009 and pembrolizumab (cohort 1) or pembrolizumab monotherapy (cohort 2). Patients randomized to the PRGN-2009 plus pembrolizumab cohort will receive PRGN-2009 via subcutaneous (SC) injection (5 x 1011 PU every 3 weeks for three administrations followed by administration each 6 weeks thereafter). Patients in the PRGN-2009 plus pembrolizumab cohort and pembrolizumab monotherapy cohort will receive pembrolizumab via intravenous (IV) infusion (400 mg every 6 weeks). Patients randomized to the pembrolizumab monotherapy cohort will be offered the option to crossover to the PRGN-2009 plus pembrolizumab cohort if certain conditions are met.

The primary objective of the Phase 2 study is to assess the objective response rate (ORR) per RECIST v1.1 following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab monotherapy. Secondary objectives include the evaluation of safety and tolerability, progression-free survival (PFS), overall survival (OS), best overall responses (BOR), Disease Control Rate (DCR), time to response and duration of response.

Precigen: Advancing Medicine with Precision
Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target the most urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on Twitter @Precigen, LinkedIn or YouTube.

About Cervical Cancer1,2
The human papillomavirus is responsible for more than 90 percent of cervical cancer cases. In 2023, there will be an estimated 13,960 new cervical cancer cases in the United States. In 2018, there were an estimated 293,394 women living with cervical cancer in the United States. Cancer stage at diagnosis determines treatment options and influences survival. The majority of cervical cancer cases are diagnosed at the local stage when the cancer has spread to other parts of the body. About 16% of cervical cancers cases are distant, when the cancer has metastasized. The 5-year survival rate for cases at the local stage is about 91% and cases at the distant stage are roughly 17%.

AdenoVerse Immunotherapy
Precigen’s AdenoVerse immunotherapy platform utilizes a library of proprietary adenovectors for the efficient gene delivery of therapeutic effectors, immunomodulators, and vaccine antigens designed to modulate the immune system. Precigen’s gorilla adenovectors, part of the AdenoVerse library, have potentially superior performance characteristics as compared to current competition. AdenoVerse immunotherapies have been shown to generate high-level and durable antigen-specific T-cell immune responses as well as an ability to boost these responses via repeat administration. Superior performance characteristics and high yield manufacturing of AdenoVerse vectors leveraging UltraVector technology allows Precigen to engineer cutting-edge investigational gene therapies to treat complex diseases.

AdenoVerse Immunotherapy Clinical Program
Precigen’s AdenoVerse immunotherapy platform is currently under clinical investigation in a Phase 1/2 study of PRGN-2009 AdenoVerse immunotherapy alone or in combination with anti-PDL1/TGF-Beta Trap (bintrafusp alfa) in patients with HPV-associated cancers (NCT04432597) and a Phase 2 study of PRGN-2012 AdenoVerse immunotherapy in patients with recurrent respiratory papillomatosis (RRP) (NCT04724980). PRGN-2012 has been granted Orphan Drug Designation in patients with RRP by the FDA.

Trademarks
Precigen, AdenoVerse, UltraVector and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

Cautionary Statement Regarding Forward-Looking Statements
Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon the Company’s current expectations and projections about future events and generally relate to plans, objectives, and expectations for the development of the Company’s business, including the timing and progress of preclinical studies, clinical trials, discovery programs and related milestones, the promise of the Company’s portfolio of therapies, and in particular its CAR-T and AdenoVerse therapies. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties, including the possibility that the timeline for the Company’s clinical trials might be impacted by the COVID-19 pandemic, and actual future results may be materially different from the plans, objectives and expectations expressed in this press release. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. For further information on potential risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in the Company’s most recent Annual Report on Form 10-K and subsequent reports filed with the Securities and Exchange Commission.

On May 31, 2023 The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) recently reported the selected abstracts for the prestigious ASCO (Free ASCO Whitepaper) 2023 Annual Meeting (Press release, Qilu Pharmaceutical, MAY 31, 2023, View Source [SID1234632301]). Four clinical research abstracts on QL1706 (iparomlimab/tuvonralimab), an innovative bifunctional antibody for immunotherapy, were accepted in the Poster Session. Two of the posters focus on the latest clinical research progress of Qilu Pharmaceutical’s QL1706 in extensive-stage small cell lung cancer (ES-SCLC) and advanced hepatocellular carcinoma (HCC).

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Study One: A Phase II Clinical Study of QL1706 in Combination with Carboplatin and Etoposide as First-line Treatment for ES-SCLC

This study is an open-label, single-arm, multicenter Phase II clinical study aimed at evaluating the safety and efficacy of QL1706 in combination with carboplatin and etoposide as first-line treatment for ES-SCLC. A total of 40 patients were enrolled in the study, with a median age of 58.5 years (range, 38-73). 87.5% of the patients were male, 80% had a history of smoking, and 90% had an ECOG performance status of 1.

As of the data cutoff date (January 16, 2023), the median treatment duration of QL1706 was 5.9 months (range, 0.7-8.9). All patients experienced at least one treatment-emergent adverse event (TEAE). A total of 32 patients (80%) experienced at least one QL1706-related treatment-related adverse event (TRAE); 15 patients (37.5%) experienced grade 3-4 TRAEs; no grade 5 TRAEs or adverse events leading to discontinuation of treatment occurred.

A total of 39 patients had at least one post-baseline tumor assessment, of whom 37 patients assessed as partial response (PR) (including 2 unconfirmed PRs) and 1 patient as stable disease (SD). The confirmed objective response rate (ORR) was 89.7% (35/39), and the disease control rate (DCR) was 97.4% (38/39) per RECIST version 1.1. The median duration of response (mDoR) was 4.5 months, and the median progression-free survival (mPFS) was 5.7 months. With a median follow-up time for overall survival (OS) of 6.2 months, the median OS has not been reached.

The results showed that QL1706 in combination with carboplatin and etoposide as first-line treatment for ES-SCLC had good tolerability and demonstrated promising efficacy.

Study Two: A Phase Ib/II Clinical Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of QL1706 or QL1604 in Patients with Advanced HCC

QL1604 is a PD-1 monoclonal antibody. The PD-1 antibody component in QL1706 is same with QL1604 in the molecular sequence, the procession of host cells construction and transfection, and the monoclonal screening process. In other words, QL1706 was furtherly engineered by incorporating the recombinant plasmid carrying the anti-CTLA-4 antibody into the QL1604 clone through transfection and monoclonal screening processes. Preliminary in vitro and in vivo factorial studies have been conducted to analyze the properties of both antibodies.

This multicenter phase Ib/II clinical trial consists of three parts. Part 1 is a safety lead-in/expansion phase. In part 2, patients were randomized to receive either QL1604 or QL1706 (5 mg/kg, every 3 weeks) in combination with bevacizumab. Initiation of Part 3 will be based on the results from Parts 1 and 2. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).

As of the data cut-off date (November 18, 2022), a total of 76 patients (50 patients in QL1706 group; 26 patients in QL1604 group) were enrolled in Parts 1 and 2. Baseline characteristics were well balanced between the two groups. The incidence of treatment-related adverse events (TRAEs) was 86% in the QL1706 group and 88.5% in the QL1604 group. The most common TRAEs in both groups were proteinuria (32.0% vs. 30.8%), followed by decreased platelet count (26.0% vs. 23.1%) and increased aspartate aminotransferase (22% vs. 19.2%). The incidence of treatment-related serious adverse events was 16% and 23.1% in the QL1706 group and the QL1604 groups, respectively. Immune-related adverse events occurred in 50% and 19.2% of patients in the QL1706 group and the QL1604 groups, respectively.

In the efficacy evaluable population, the QL1706 group had an ORR of 38.3% (18/47) and a DCR of 74.5%. The QL1604 group had an ORR of 15.4% (4/26) and a DCR of 69.2%. The median PFS were 6.7 months and 5.4 months in the QL1706 group and the QL1604 groups, respectively. The median overall survival has not been reached in either group.

These results suggest that QL1706, in combination with bevacizumab, resulted in a higher ORR and longer PFS compared to QL1604 when used as first-line treatment for advanced HCC. These findings support further investigation of QL1706 plus bevacizumab for first-line treatment of advanced HCC in a phase III clinical trial.

On May 31, 2023 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported that the first patient has been dosed in a Phase 1 study of CDX-585 (Press release, Celldex Therapeutics, MAY 31, 2023, View Source [SID1234632298]). CDX-585 combines highly active PD-1 blockade with anti-ILT4 blockade to overcome immunosuppressive signals in T cells and myeloid cells. Celldex plans to develop CDX-585 for the treatment of solid tumors either as monotherapy or in combination with other oncologic treatments. CDX-585 is the first compound from Celldex’s research and collaboration agreement with Biosion, Inc. and combines Celldex’s ILT4 mAb with Biosion’s PD-1 mAb.

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"We are excited to advance CDX-585 into clinical development as we continue to build our experience with our bispecific platform," said Diane C. Young, M.D, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. "Targeting both myeloid and T cell checkpoints with a bispecific is a novel approach that we believe could provide benefit for patients that are either refractory to or not likely to benefit from PD-1 blockade alone."

This open-label, multi-center, intravenous study of CDX-585 is being evaluated in patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy. The dose-escalation phase of the study (n=~30 patients) is designed to determine a maximum tolerated dose (MTD) and to select CDX-585 dose(s) for future evaluation in tumor specific expansion cohorts. In the first phase, increasing doses of CDX-585 will be administered intravenously (0.03 mg/kg up to 10.0 mg/kg) every 2 weeks until confirmed disease progression, intolerance, or for a maximum of 2 years. In the second phase, potential expansion cohorts will evaluate the safety, tolerability and biologic effects, including anti-tumor activity, of selected dose level(s) of CDX-585 in specific tumor types.

Preclinical data(opens in a new tab) recently presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 demonstrated that CDX-585 is a potent antagonist of both PD-1 and ILT4, and CDX-585 is more potent than the combination of PD-1 and ILT-4 mAbs in several model systems. CDX-585 also demonstrated a good pharmacokinetic profile and no evidence of toxicity supporting initiation of clinical development.

For additional information on this trial (NCT05788484), please visit www.clinicaltrials.gov(opens in a new tab).

About CDX-585
CDX-585 is a dual targeting PD-1/ILT4 bispecific antibody from Celldex’s bispecific antibody platform. Expression of ILT4 in several tumor types is associated with poor outcome and in preclinical models, antagonist antibodies to ILT4 have demonstrated immune enhancing and antitumor effects. Preclinical studies have shown that CDX-585 is a potent antagonist of both PD-1 and ILT4, and CDX-585 is more potent than the combination of PD-1 and ILT-4 mAbs in several model systems. CDX-585 is being developed as part of a research and collaboration agreement with Biosion, Inc. and combines Celldex’s ILT4 mAb with Biosion’s PD-1 mAb.

On May 31, 2023 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated oral targeted agents to treat hematologic malignancies, reported that the company management team will provide a clinical update on Saturday, June 10, 2023, at 12:00 PM EST / 6:00 PM CEST, in conjunction with EHA (Free EHA Whitepaper) 2023 International Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Frankfurt, Germany (Press release, Aptose Biosciences, MAY 31, 2023, View Source [SID1234632297]). The webcast event will include an interim review of Aptose’s lead compound tuspetinib, a myeloid kinase inhibitor, currently being tested as a monotherapy and in combination with venetoclax in the phase 1/2 APTIVATE trial.

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Tuspetinib, administered as a once-daily oral tablet, is a precision targeted kinase inhibitor designed to suppress a select handful of kinases known to drive proliferation of acute myeloid leukemia (AML) while maintaining a favorable safety profile. Aptose management will highlight additional insights from the completed Phase 1/2 dose escalation clinical trial of tuspetinib and review early trends from the ongoing APTIVATE trial.

Aptose Clinical Update Webcast Details

Date & Time: Saturday, June 10, 2023, 12:00 PM ET

Participant Webcast Link: Link

Participant Dial-in:

Toll Free Investors Dial: 1-877-407-9039

Toll/International Investors Dial: 1-201-689-8470

Conference ID: 13739137

The slides will be available on Aptose’s website here and the webcast of the presentation will be archived shortly after the conclusion of the event.

In addition, an abstract on tuspetinib was recently published in EHA (Free EHA Whitepaper)’s open access library here:

Abstract: PB1766

Title: IN VITRO ACQUIRED RESISTANCE TO THE ORAL MYELOID KINASE INHIBITOR TUSPETINIB CREATES SYNTHETIC LETHAL VULNERABILITY TO VENETOCLAX

Session Title: Acute myeloid leukemia – Biology & Translational Research

Tuspetinib (TUS) is a once daily, oral agent that potently inhibits JAK1/2, SYK, RSK1/2, wildtype and mutant forms of FLT3, and mutant forms of KIT kinases, thereby simultaneously suppressing multiple oncogenic signaling pathways that mediate resistance to various drugs. TUS as a single agent has generated complete remissions in relapsed/refractory (R/R) acute myeloid leukemia (AML) patients with diverse mutations and demonstrated favorable safety in a Phase 1 trial (NCT03850574). TUS is now in a Phase 1/2 expansion trial (APTIVATE) for R/R AML patients with high unmet need as a monotherapy and as a doublet in combination with venetoclax. The clinical activity against diverse mutational subpopulations led us to investigate alterations in AML cells that may give rise to TUS resistance, and to understand the sensitivity of resistant isolates to venetoclax and other agents used to treat AML.

Resistance to TUS in MOLM-14 cells required prolonged high-level drug exposure, but ultimately yielded a stable phenotype. Strikingly, acquired TUS resistance generated a synthetic lethal vulnerability in which the cells were unusually hypersensitive to venetoclax. This suggests that concurrent administration of TUS and venetoclax may be advantageous clinically as TUS and venetoclax could act in concert to discourage the emergence of drug resistance during treatment.

For full published abstract, please visit: View Source

On May 31, 2023 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL RNAi platform technology is designed to make immune cells more effective in killing tumor cells, reported that it has entered into definitive agreements for the issuance and sale of an aggregate of 233,646 of its shares of common stock at a purchase price of $4.28 per share in a registered direct offering (Press release, Phio Pharmaceuticals, MAY 31, 2023, View Source [SID1234632296]). In a concurrent private placement, Phio has also agreed to issue and sell an aggregate of 700,935 of its shares of common stock (or common stock equivalents), at the same purchase price of $4.28 per share (or common stock equivalent) as in the registered direct offering. In addition, the Company has agreed to issue in the offerings unregistered Series A warrants to purchase up to an aggregate of 934,581 shares of common stock and unregistered Series B warrants to purchase up to an aggregate of 934,581 shares of common stock. The registered direct offering and the private placement were priced at-the-market under Nasdaq rules. The offerings are expected to close on or about June 2, 2023, subject to the satisfaction of customary closing conditions.

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Logo – View Source

H.C. Wainwright & Co. is acting as the exclusive placement agent for the offerings.

Each series of warrants will have an exercise price $4.03 per share and become exercisable immediately upon issuance. The Series A warrants have a term of five and one-half years from the date of issuance and the Series B warrants have a term of eighteen months from the date of issuance.

The gross proceeds to the Company from the concurrent offerings are expected to be approximately $4 million, before deducting the placement agent’s fees and other offering expenses payable by Phio. Phio currently intends to use the net proceeds from the offerings for the development of its immuno-oncology programs, working capital and general corporate purposes.

The shares of common stock (or common stock equivalents) offered in the registered direct offering (but excluding the securities offered in the private placement and the shares of common stock underlying the unregistered warrants issued in the registered direct offering) are being offered and sold by the Company pursuant to a "shelf" registration statement on Form S-3 (Registration No. 333-256100), including a base prospectus, previously filed with the Securities and Exchange Commission (SEC) on May 13, 2021 and declared effective by the SEC on May 21, 2021. The offering of the shares of common stock (or common stock equivalents) to be issued in the registered direct offering are being made only by means of a prospectus supplement that forms a part of the registration statement. A final prospectus supplement and an accompanying base prospectus relating to the registered direct offering will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the final prospectus supplement and accompanying base prospectus may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

The offer and sale of the securities in the private placement and the unregistered warrants described above are being made in a transaction not involving a public offering and have not been registered under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Securities Act") and/or Rule 506(b) of Regulation D promulgated thereunder and, along with the shares of common stock underlying the unregistered warrants, have not been registered under the Securities Act or applicable state securities laws. Accordingly, the securities in the private placement, the unregistered warrants and underlying shares of common stock may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws.

Phio has agreed to file an initial registration statement with the SEC covering the resale of the securities to be issued in the private placement no later than 10 days following May 31, 2023 and to use commercially reasonable efforts to have the registration statement declared effective as promptly as practical thereafter, and in any event no later than 70 days after May 31, 2023 in the event of a "full review" by the SEC.