On December 12, 2024 iTeos Therapeutics, Inc. (Nasdaq: ITOS), a clinical-stage biopharmaceutical company pioneering the discovery and development of a new generation of immuno-oncology therapeutics for patients, reported the presentation of clinical, translational, and preclinical data from its adenosine A2A receptor (A2AR) antagonist program, inupadenant, including interim data from the dose escalation portion of A2A-005, the Phase 2 trial assessing inupadenant and platinum-doublet chemotherapy in post-immunotherapy metastatic non-small cell lung cancer (NSCLC) patients, at the European Society for Medical Oncology Immuno-Oncology (ESMO IO) Congress 2024 (Press release, iTeos Therapeutics, DEC 12, 2024, View Source [SID1234649083]).

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"We believe our presentations at ESMO (Free ESMO Whitepaper) IO on the adenosine pathway demonstrate the strong efforts our research and discovery team have put into understanding this immunosuppressive mechanism," said Michel Detheux, Ph.D., president and chief executive officer of iTeos. "While the initial signal for inupadenant’s RP2D in the A2A-005 trial compared to chemotherapy alone is encouraging and supports its differentiated, insurmountable profile, we as well as our scientific and clinical advisory boards believe it does not meet sufficient level of clinical activity to warrant further investment. We remain committed to focusing our resources on developing differentiated, first- or best-in-class therapies and look forward to providing updates on our pipeline in 2025."

Mini Oral Sessions
Title: Inupadenant Combined with Chemotherapy in Patients with Non-Squamous NSCLC Progressing On or After Immune Checkpoint Inhibitor Therapy: Results from Dose-Finding Part of the A2A-005 Trial
Summary: As of the October 29, 2024 data cutoff, the topline data from the dose escalation portion of A2A-005 presented at the ESMO (Free ESMO Whitepaper) IO Congress were based on 36 patients eligible for safety and efficacy evaluation. Patients received inupadenant at 40mg, 60mg, or 80mg twice daily (BID) in combination with carboplatin/pemetrexed. All patients had a minimum follow-up of 6 months. Patient baseline characteristics were balanced across arms, with a slight imbalance of more patients with brain metastases in the 40mg and 80mg cohorts and ECOG status 0 favoring the 80mg cohort.

The primary endpoint of the safety of inupadenant in combination with carboplatin/pemetrexed was observed to be manageable and tolerable, with no dose dependent toxicities.
The secondary endpoint of ORR was 63.9% across all patients (53.3% at 40mg, 66.7% at 60mg, and 73.3% at 80mg).
The secondary endpoint of mPFS was 7.7 months across all patients (5.6 months at 40mg and 6.6 months at 60mg; mPFS remains unreached at 80mg).
The exploratory biomarker of CXCL13, a B-cell chemokine and lymphoid structure marker associated with clinical activity, was observed to be restored by inupadenant after depletion by chemotherapy, with quicker restoration kinetics in patients with PFS greater than 6 months.
As of the data cutoff, 8 patients remained on treatment (1 at 40mg, 1 at 60mg, and 6 at 80mg). The median follow-up was 9.7 months (10.6 months at 40mg, 13.1 months at 60mg, and 8.2 months at 80mg).

Response Measure Inupadenant 40mg + carboplatin / pemetrexed BID Inupadenant 60mg + carboplatin / pemetrexed BID Inupadenant 80mg + carboplatin / pemetrexed BID Overall
(N=15) (N=6) (N=15) (N=36)
ORR, % 53.3% 66.7% 73.3% 63.9%
n
(95% CI) n=8
(26.6–78.7) n=6
(22.3–95.7) n=15
(44.9–92.2) n=36
(46.2–79.2)
Complete response, n (%) 0 0 2 (13.3%) 2 (5.6%)
Partial response, n (%) 8 (53.3%) 4 (66.7%) 9 (60.0%) 21 (58.3%)
Stable disease, n (%) 7 (46.7%) 1 (16.7%) 3 (20.0%) 11 (30.6%)
Progressive disease, n (%) 0 0 1 (6.7%) 1 (2.8%)
Not evaluable/no assessment, n (%) 0 1 (16.7%) 0 1 (2.8%)
mPFS, months 5.6 6.6 NC 7.7
Event n (%)
(95% CI) 13 (86.7%)
(4.1-8.3) 5 (83.3%)
(0.4-NC) 6 (40.0%)
(4.9-NC) 24 (66.7%)
(5.1-11.0)
Landmark 6-Month PFS % 46.7%
(21.2-68.7) 50.0%
(11.1-80.4) 64.6%
(34.7-83.5) 54.5%
(36.8-69.1)
CI, confidence interval; NC, not calculable

Title: The A2AR Antagonist Inupadenant Promotes Humoral Responses in Patients
Summary: Based on monotherapy clinical and translational data, inupadenant demonstrated modulation of humoral responses in patient blood and tumor tissue, supporting our previous finding that expression of antibody-secreting cells (ASCs) in tumor tissue is associated with non-progression in patient disease. Furthermore, CXCL13 expression, a protein involved in immune cell recruitment, activation, and adaptive immune response regulation, increased in patients treated with inupadenant and more rapidly and extensively in non-progressors compared to progressors. These findings confirm inupadenant plays a key role in B cell maturation restoration and may play a substantial role in delaying progression in end-stage patients.

Poster Sessions
Title: The A2AR Antagonist Inupadenant Promotes Humoral Responses in Preclinical Models
Summary: In preclinical models, inupadenant counteracted the A2AR-mediated inhibition of B cell maturation into ASCs and immunoglobulin production in both in vitro and ex vivo systems by modulating B cells at the level of the germinal center (GC). These findings suggest that inupadenant restores or even enhances B cell maturation towards ASCs and GC reactions in both secondary lymphoid organs as well as the tumor in the presence of A2AR signaling. Furthermore, this process is essential for producing high-affinity antibodies and potentially for sustained anti-tumor immunity.

Title: A Novel Tumor Adenosine Signature to Guide Indication Selection for Adenosine Pathway inhibitor
Summary: Based on the spatial quantification of adenosine in human tumors, we developed the first adenosine gene signature, demonstrating its potential for indication selection. This new signature, derived from 249 differentially expressed genes (DEGs) associated with metabolism and immune activation, showed high predictive power across tumor types. Furthermore, the adenosine signature was higher in tumors compared to healthy tissue and exhibited variable expression and prognostic value across tumor subtypes. These findings suggest that the adenosine signature represents a powerful tool for prioritizing tumor types which may benefit most from adenosine-targeting therapies and for understanding the mechanisms of adenosine-mediated immunosuppression.

On December 12, 2024 NEC Bio Therapeutics reported 24-week promising interim results from an ongoing Phase 1 basket clinical trial of an orally administered cancer vaccine, NECVAX-NEO1, used in combination with checkpoint inhibitors (CPI) for treating patients with solid tumors (Press release, NEC, DEC 12, 2024, View Source [SID1234649050]). The findings are being presented in a poster at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress in Geneva, Switzerland from December 11 to 13, 2024.

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NECVAX-NEO1 is a personalized bacteria-based oral DNA therapeutic vaccine, developed using AI prediction of the most immunogenic patient-specific neoepitopes. This vaccine is designed to activate the patient’s immune system, prompting a T-cell response that can precisely target and eliminate tumor cells based on the individual’s unique neoantigens.

In the phase 1 study, 5 patients with melanoma, renal cell cancer, or head and neck cancer, who have been on CPI treatment for at least three months, were treated with NECVAX-NEO1. The safety run-in phase showed no treatment-related toxicities, allowing a dose increase. An ELISPOT response was induced by 68% of neoepitopes, with 40% of patients showing significant neoantigen-specific signals. After a 24-week treatment period, 80% of patients had a stable disease status, indicating a high disease control rate.

On the results of the clinical study, Dr. Heinz Lubenau, CEO of NEC Bio Therapeutics, commented, "We are very excited about our first proof-of-concept data showing signs of promising immunogenicity and associated biomarker changes in patients. This is very encouraging, especially in light of new clinical trials currently ongoing at various locations in early and late-stage cancer patients. We are looking forward to generating more data for NECVAX-NEO1 as an additional treatment option for patients with difficult to treat cancer in the future."

Motoo Nishihara, Corporate Executive Vice President and CTO of NEC Corporation, further commented, "We are certainly excited to present the progress of the NECVAX-NEO1 trial demonstrating safety and signs of immunogenicity. NECVAX-NEO1 is the first cancer vaccine asset to be clinically developed at NEC. This development ties in with the larger NEC mission of providing healthcare solutions globally using the state of art technologies developed in-house."

Details of the poster are below:

Poster title: Oral DNA vaccination targeting personalised neoantigens in immune checkpoint inhibitor treated solid tumor patients – Interim results.

Authors: Domas Vaitiekus, E. Juozaityte, L. Puzauskienė, S. Tulyte, L. Gatijatullin, M. Platten, I. Poschke, I.Hulsmeyer, A. Kuhn, A. Aranguren, H. Lubenau, H. Fontenelle, B. Simovski, Y. Yamashita, C.Chaput, A. Meiser, V. Urbonas

Poster Number: 160P

Date: 12 December 2024

The poster may also be found here: Link to PDFNEC Bio website. Trial details can also be viewed at: new windowNCT05354323

NECVAX-NEO1 is currently under evaluation at additional clinical trial sites in Lithuania, Germany, and Spain. These sites are actively recruiting patients and are open for enrollment.

On December 12, 2024 ALX Oncology Holdings Inc. ("ALX Oncology" or "the Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives, reported that the company will host a virtual event on Tuesday, December 17, at 5:00 AM PST / 8:00 AM EST to discuss the first data from a Phase 1b/2 clinical trial evaluating the company’s investigational CD47-blocker evorpacept in combination with Jazz Pharmaceuticals’ zanidatamab in heavily pretreated patients with metastatic breast cancer (Press release, ALX Oncology, DEC 12, 2024, View Source [SID1234649067]). The data were featured today in a spotlight poster presentation at the 2024 San Antonio Breast Cancer Symposium (SABCS). The poster is now available on the ALX Oncology site under Publications.

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During the virtual company event, Alberto J. Montero, MD, MBA, Clinical Director, Breast Cancer Medical Oncology Program, Diana Hyland Endowed Chair for Breast Cancer, and Professor of Medicine at University Hospitals Seidman Cancer Center, Case Western Reserve University, and the study’s principal investigator, will provide an overview of the data presented at SABCS 2024 and participate in a fireside chat with Alan Sandler, MD, ALX Oncology’s Chief Medical Officer. Jason Lettmann, Chief Executive Officer at ALX Oncology, will provide opening and closing remarks, highlighting progress and upcoming milestones for the company’s evorpacept clinical program.

The event will be webcast live and can be accessed by visiting the Investors section of ALX Oncology’s website at www.alxoncology.com and selecting Events under News and Events. To participate in the live event, please register using this link: View Source An archived webcast will be available following the event.

On December 12, 2024 Candel Therapeutics, Inc. ("Candel") (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported the pricing of an underwritten public offering of 10,000,001 shares of its common stock at a price to the public of $6.00 per share and pre-funded warrants to purchase up to an aggregate of 3,333,333 shares of its common stock at a price to the public of $5.99 per pre-funded warrant to purchase one share of the common stock, which represents the per share public offering price for the common stock less the $0.01 per share exercise price for each such pre-funded warrant (Press release, Candel Therapeutics, DEC 12, 2024, View Source [SID1234649084]). The gross proceeds from the offering to Candel are expected to be approximately $80 million, before deducting underwriting discounts and commissions and other offering expenses. The offering is expected to close on or about December 16, 2024, subject to customary closing conditions. In addition, Candel has granted the underwriters a 30-day option to purchase up to 2,000,000 additional shares of common stock at the public offering price, less the underwriting discount.

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Candel intends to use the net proceeds from the offering to continue the development of its product candidates, including preparing submission of a Biologics License Application for CAN-2409 in prostate cancer and for general corporate purposes.

Citigroup, BofA Securities and Canaccord Genuity are acting as joint bookrunning managers for the offering. H.C. Wainwright & Co. is acting as lead manager for the offering.

A shelf registration statement relating to the shares of common stock offered in the public offering described above was filed with the Securities and Exchange Commission (the "SEC") on August 5, 2022 and declared effective by the SEC on August 12, 2022. The offering is being made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. A final prospectus supplement and accompanying prospectus will be filed with the SEC. When available, copies of the final prospectus supplement and the accompanying prospectus may also be obtained by contacting Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, or telephone: 1-800-831-9146; BofA Securities, NC1-022-02-25, 201 North Tryon Street, Charlotte, North Carolina 28255-0001, Attention: Prospectus Department, email: [email protected]; or Canaccord Genuity LLC, Attention: Syndication Department, 1 Post Office Square, 30th Floor, Boston, MA 02109, or by email at [email protected].

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

On December 12, 2024 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, reported the publication of preclinical data for Aptose’s lead hematology compound tuspetinib (TUS) in Cancer Research Communications, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Aptose Biosciences, DEC 12, 2024, View Source [SID1234649068]).

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The publication, entitled "Preclinical development of tuspetinib for the treatment of acute myeloid leukemia," is the first preclinical profiling of tuspetinib, a well-tolerated, once daily, oral kinase inhibitor currently in clinical development for treatment of acute myeloid leukemia (AML). The publication defines TUS activities on select oncogenic signaling targets, demonstrates enhanced activity and safety of TUS when combined with other agents, and illustrates synthetic lethality when combined with venetoclax (VEN). Pharmacokinetic and toxicology studies revealed that TUS is readily absorbed and achieves plasma concentrations sufficient to inhibit the target kinases, it has a plasma half-life that supports once daily dosing, and it demonstrates a favorable safety profile.

Aptose is now enrolling newly diagnosed AML patients in a Phase 1/2 clinical study to receive the tuspetinib + venetoclax + azacitidine (TUS+VEN+AZA) triplet combination (NCT03850574). Clinical studies in patients with relapsed or refractory AML receiving TUS single agent or the TUS+VEN combination have been completed.

"The non-clinical findings presented in the publication suggest that TUS will demonstrate favorable safety and a breadth of antileukemic activity across AML patient populations with a diversity of adverse mutations, and the initial clinical data is bearing that out," said William G. Rice, Chairman, President and Chief Executive Officer. "We are eager for the next set of data in our triplet combination trial of TUS+VEN+AZA."

Key findings:

Tuspetinib inhibits a defined cluster of oncogenic signaling kinases operative in AML
TUS inhibits SYK, JAK1/2, RSK2, mutant KIT, and wild type and mutant forms of FLT3
TUS potently killed AML lines (GI50 = 1.3 to 5.2 nM) and Ba/F3 cells expressing wildtype (GI50 = 9.1 nM) or various mutant forms of FLT3 (GI50 = 2.5 – 56 nM)
TUS dampens stroma-induced activation of FLT3-ITD signaling in AML cells
TUS prolongs survival in multiple AML models
Oral TUS markedly extended survival in subcutaneously and orthotopically inoculated xenograft models of FLT3 mutant human AML, was well tolerated, and delivered enhanced activity when combined with venetoclax or 5-azacytidine
TUS combines effectively with other classes of agents to kill AML cells with mutations in RAS and other difficult-to-treat adverse mutations
TUS was 2.1-15-fold and a 4.5-13-fold more potent than gilteritinib at blocking fibrinogen and immunoglobulin-mediated activation of SYK in KG-1a cells
The most notable observation was the marked and unexpected synthetic lethal vulnerability to venetoclax and two MCL1 inhibitors in the TUS-resistant cells