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 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 Phio Pharmaceuticals Corp. (NASDAQ: PHIO) is a clinical-stage biotechnology company developing therapeutics that use its INTASYL siRNA gene silencing technology designed to make the body’s immune cells more effective in killing cancer cells reported its manuscript, Self-delivering RNAi Immunotherapeutic PH-762 Silences PD-1 to Generate Local and Abscopal Anti-tumor Efficacy, has been published in the December, 2024 issue of Frontiers in Immunology (Press release, Phio Pharmaceuticals, DEC 12, 2024, View Source [SID1234649082]).

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The article presents preclinical proof-of-concept data for PH-762, an INTASYL compound designed to silence PD-1, is currently in clinical development for advanced cutaneous malignancies. Phio recently presented data from its second cohort in its on-going Phase 1b clinical trial showing one patient with cutaneous squamous cell carcinoma in the 2nd cohort achieved a complete response (100% tumor clearance) while a second patient with squamous cell carcinoma achieved a partial response (90% tumor clearance).

Frontiers in Immunology is dedicated to propelling advancements in the field of Immunology. The Editor-in-Chief is Luigi Daniele Notarangelo, Director of the Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIH), and Senior Researcher at Boston Children’s Hospital, Harvard Medical School.

"We are delighted to see this publication which presents a comprehensive summary of INTASYL’s uniqueness addressing its selective gene targeting, potent silencing, and is a promising candidate for treatment of solid tumors," said Robert Bitterman, CEO, Phio Pharmaceuticals.

On December 12, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported positive data from its MYTHIC Phase 1 gynecologic expansion clinical trial evaluating the combination of lunresertib and camonsertib (Lunre+Camo) at the recommended Phase 2 dose (RP2D) in patients with endometrial cancer and platinum-resistant ovarian cancer (PROC) harboring lunre-sensitizing biomarkers (Press release, Repare Therapeutics, DEC 12, 2024, View Source [SID1234649081]).

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Lunresertib is a first-in-class precision oncology small molecule PKMYT1 inhibitor which targets cell cycle regulation in Lunre BM+ tumors (CCNE1 amplifications or FBXW7 or PPP2R1A deleterious alterations). Camonsertib is a potential best-in-class oral small molecule inhibitor of ATR, a critical component of the DNA damage response pathway.

"We are encouraged by the strong response and the clear benefit we observed in patients with endometrial and platinum-resistant ovarian cancers in the MYTHIC clinical trial," said Lloyd M. Segal, President and Chief Executive Officer of Repare. "These patients need new treatment options and our results support the potential for Lunre+Camo to make a real, positive difference if approved, particularly as a chemotherapy alternative. We have positive feedback from regulatory agencies in both the US and Europe and we look forward to getting started on a registrational Phase 3 trial of Lunre+Camo in endometrial cancer in the second half of 2025."

The MYTHIC clinical trial (NCT04855656) is a first-in-human, global, open-label Phase 1 dose-escalation clinical trial to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of Lunre+Camo in patients with advanced solid tumors. As of the data cut-off date of November 14, 2024, 51 evaluable patients were enrolled in the gynecologic cancer expansion cohort of the MYTHIC trial.

Across all tumor types treated at the optimized RP2D (n=67), Lunre+Camo therapy demonstrated a favorable and differentiated tolerability profile when compared to current and emerging therapies. The most common adverse event was anemia (26.9%, Grade 3).

Key Cohort Clinical Findings

Endometrial Cancer Patients:

The 27 evaluable patients with endometrial cancer had a median age of 67 years. All patients exhibited high-risk profiles:

•
100% of patients have undergone prior platinum therapy

•
77.8% of patients received immune checkpoint inhibitors

•
59% of patients received the combination as a fourth line of therapy or beyond

•
18.5% of patients had carcinosarcoma

•
85% of tumors had p53 mutations

•
No tumors with microsatellite instability (MSI)-high status were enrolled indicating proficient mismatch repair (pMMR) status
•
Within the Lunre BM+ subset: 56% of tumors had PPP2R1A mutations; 22% carried FBXW7 mutations; 15% had CCNE1 amplification; and 7% of tumors had multiple mutations

Key efficacy outcomes in evaluable patients with endometrial cancer (N=27):

•
ORR was 25.9% (confirmed ORR in 5 out of 7 patients)

•
Clinical benefit was observed in 48.1% of patients, with responses frequently occurring after 12 weeks or more

•
At the 24-week landmark analysis, nearly half of patients experienced durable clinical benefit (24-week PFS [PFS24w] = 43% [95% CI, 21-63%])

Platinum-Resistant Ovarian Cancer Patients:

The 24 evaluable patients with PROC had a median age of 63 years. All patients exhibited high-risk profiles:

•
100% of patients were platinum-resistant or platinum ineligible

•
45.8% of patients had received prior PARP inhibitors

•
70.8% of patients had received prior bevacizumab

•
54% of patients received the combination as a fourth line of therapy or beyond

•
100% of tumors had p53 mutations

•
Within the Lunre BM+ subset: 87.5% of tumors had CCNE1 amplification; 4.2% had FBXW7 mutations; 4.2% had PPP2R1A mutations; and 4.2% of tumors had multiple mutations

Key efficacy outcomes in evaluable patients with PROC (N=24):

•
ORR was 37.5% (confirmed ORR in 4 out of 9 patients)

•
Clinical benefit was observed in 79% of patients

•
PFS at the 24-week landmark analysis was (PFS24w = 45% [95% CI, 22-66%]).

"Those patients with recurrent gynecologic cancers have limited treatment options as tumors often become resistant to standard of care therapy," said Brian Slomovitz, MD, MS, FACOG, Director, Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount Sinai Medical Center. "They urgently need new treatment options. Repare’s differentiated, biomarker-driven approach addresses this population and may offer a solution. These data support the potential of Lunre+Camo as a new treatment option to fill this unmet need for patients with endometrial and platinum-resistant ovarian cancers."

Repare has consulted with both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency, who have provided guidance into the Company’s registrational development plans for Lunre+Camo in gynecologic tumors, including assessment of the contribution of components, dose and schedule and preliminary alignment on the proposed registrational development approach. Repare plans to provide the final Phase 3 trial protocols for regulatory clearance imminently and intends to start the first Phase 3 Lunre+Camo trial in endometrial cancer in the second half of 2025. Additionally, the Company expects to initiate a small contribution of components trial in up to 40 patients with endometrial cancer in the first quarter of 2025.

"The results of the MYTHIC clinical trial increase our confidence in the potential to bring Lunre+Camo to patients living with this aggressive subset of recurrent endometrial cancer," said Maria Koehler, MD, PhD, Chief Medical Officer of Repare. "We are deeply grateful to the patients and investigators who participated in this trial, and we look forward to building on these promising data through the registrational clinical trials using Lunre+Camo as a potential new standard of care for those patients, if approved."

Conference Call and Webcast:

Repare will host a conference call and webcast today, December 12, at 4:30 p.m. ET to discuss the results. Repare’s executive management team will be joined by Brian Slomovitz, MD, MS, FACOG, Director, Gynecologic Oncology, Co-chair of the Cancer Research Center, Mount Sinai Medical Center.

To access the call, please dial (646) 357-8785 (U.S. and Canada) or (800) 836-8184 (international) at least 10 minutes prior to the start time and ask to be joined to the Repare Therapeutics call. A live webcast and presentation materials will be available in the Investor section of the Company’s website at View Source A webcast replay will also be archived for at least 30 days.

On December 12, 2024 Synaffix B.V., a Lonza company (SIX:LONN) focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index, reported that it has entered into a licensing agreement with Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs (Press release, Synaffix, DEC 12, 2024, View Source [SID1234649080]).

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Synaffix gives Elevation Oncology global access to its clinical stage, site-specific ADC technology platform, including GlycoConnect antibody conjugation technology, HydraSpace polar spacer technology, as well as the toxSYN linker-payload, SYNstatin E, which enables the transformation of Elevation Oncology’s antibody into a differentiated ADC with best-in-class potential.

Under the terms of the agreement, Synaffix is eligible to receive up to USD 368 million in upfront and clinical, regulatory, and commercial milestone payments, plus tiered royalties on net sales. Synaffix is responsible for manufacturing the components related to its proprietary technologies, and Elevation Oncology is responsible for the research, development, manufacturing, and commercialization of the ADC.

Peter van de Sande, Head of Synaffix, said: "As a dedicated partner in the ADC space, Synaffix is excited to collaborate with Elevation Oncology to push the boundary of ADC innovation. With our state-of-the-art ADC technology platform and established supply chain, Elevation is well-positioned to accelerate the development of its differentiated HER3 ADC."

David Dornan, Chief Scientific Officer at Elevation Oncology, commented: "Our partnership with Synaffix enables us to build a HER3 ADC candidate with best-in-class potential, which leverages Synaffix’s state-of-the-art site-specific conjugation and differentiated linker-payload for a potentially improved safety and efficacy profile. We look forward to advancing our pipeline as we work toward transforming the care and treatment of patients living with solid tumors that express HER3."