On December 12, 2024 Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel therapies that address emerging targets in oncology, reported an update on clinical progress and data in the Phase II program RVU120, its fully-owned first-in-class dual CDK8/19 inhibitor, currently being developed to treat hematologic malignancies (Press release, Ryvu Therapeutics, DEC 12, 2024, View Source [SID1234649088]).

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Paweł Przewięźlikowski, co-founder and Chief Executive Officer of Ryvu Therapeutics said:

– 2024 has been transformative for RVU120 development plan in hematologic malignancies, marked by activating over 100 clinical sites across Europe and North America. By the year-end, we expect to enroll almost 100 patients across all four Phase II studies launched this year, demonstrating the scale and efficiency of our global clinical efforts. This progress aligns with the budget we planned back in 2023. As we enter 2025, we are poised to carry strong enrollment momentum and the ambition to generate informative efficacy readouts in the coming months.

KEY OVERALL UPDATES

Ryvu successfully launched all four RVU120 Phase II clinical studies planned for 2024: RIVER-52, RIVER-81, POTAMI-61 and REMARK – with all studies progressing on track toward key efficacy analyses in H1 2025.
Study sites: As of December 11, 2024, Ryvu activated 106 clinical sites in Poland, Italy, Spain, France, Germany, and Canada. The Company estimates that across all four RVU120 Phase II studies, 113 sites will have been activated by the end of 2024.
Study enrollment: Enrollment is accelerating, with 78 patients enrolled as of December 11, 2024. Ryvu anticipates dosing ~100 patients by year-end. The pace of recruitment has picked up significantly since September 2024, with nearly three times as many patients expected to be treated in Q4 2024 alone compared to the combined total from Q1 to Q3.
Safety: RVU120 demonstrates a favorable safety profile compared to other drugs used to treat acute myeloid leukemia (AML).
Efficacy:
o In the RIVER-81 study (RVU120 in combination with venetoclax in patients with relapsed/refractory AML, r/r AML, who have failed a previous venetoclax/HMA-based regimen), within eight patients treated with RVU120 at 250 mg (RP2D) that had at least one evaluable post-baseline assessment, one patient achieved a complete remission (CR), and another patient achieved a significant blast reduction. Part 1 of the study (combination dose escalation) was completed, and Part 2 is currently enrolling at the full doses of RVU120 (250 mg) and venetoclax (400 mg).
o In the RIVER-52 study (RVU120 as a monotherapy in patients with r/r AML and high-risk myelodysplastic syndromes; HR-MDS), one of two evaluable patients in cohort 2 (NPM1 mutation) achieved a 50% blast reduction, while disease stabilizations and reduction of peripheral blasts were observed in patients in cohort 3 (DNMT3A mutation).
o Key efficacy readouts in both RIVER-52 and RIVER-81 studies and the first efficacy data in the POTAMI-61 and REMARK trials are expected in H1 2025.
All studies align with the originally planned budgets, while Ryvu’s cash runway guidance to Q1 2026 remains unchanged.
Hendrik Nogai, M.D., Chief Medical Officer of Ryvu Therapeutics said:

– The growing body of evidence confirms that RVU120 appears to have a favorable safety profile compared to other drugs used for treating similar hematologic malignancies, both in monotherapy and in combination with venetoclax. The RIVER-81 study has progressed to Part 2 with positive signals, including a complete remission in one patient treated with RVU120 at a dose of 250 mg. Similarly, the RIVER-52 study provides early signs of efficacy, but more data are needed to evaluate RVU120 in the targeted population. With increased enrollment, we expect to obtain a representative number of patients in H1 2025. In this timeframe, we also plan to obtain the first efficacy data in the POTAMI-61 and REMARK studies.

ABOUT RVU120 AND UPDATES BY PHASE II STUDY

RVU120 is a selective, first-in-class dual CDK8/19 kinase inhibitor developed by Ryvu Therapeutics. RVU120 as monotherapy has demonstrated clinical activity in a Phase Ib (RIVER-51) study, where 50% of evaluable patients with r/r AML or HR-MDS achieved clinical benefit, including a complete remission, a morphologic leukemia-free state, transition to a bone-marrow transplant, two-year disease stabilization, multiple clinically significant blast reductions, hematologic improvements, and reduction of bone marrow fibrosis. In particular, early signs of efficacy were observed in patients with NPM1 and DNMT3A mutations, as well as in patients with HR-MDS. RVU120 achieved target engagement of 50-70% at a dose of 250 mg, which was selected as a recommended Phase II dose (RP2D). These levels are expected to produce robust antileukemic efficacy in Phase II studies.

Following the announcement of the updated development plan for the RVU120 program in October 2023, Ryvu successfully launched all four planned Phase II studies in hematologic malignancies in 2024 (RIVER-52, RIVER-81, POTAMI-61 and REMARK). Ryvu initiated a global clinical program with the activation as of December 11, 2024, of 106 sites in Poland, Italy, Spain, France, Germany and Canada.

RIVER-81: Phase II study of RVU120 in combination with venetoclax administered to patients with AML who are relapsed or refractory to prior therapy with venetoclax and a hypomethylating agent (NCT06191263).

The RIVER-81 study is a multicenter, open-label clinical trial that aims to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD).

The study is divided into three parts. Part 1 aims to identify safe and tolerated doses of RVU120 and venetoclax when used in combination through dose escalation of both study drugs. In Part 2, the selected doses will be evaluated for safety and efficacy in a larger group of patients. Part 3 is confirmatory. The planned overall enrollment for the study is approximately 35 to 98 patients, depending on the decision on the final scope of the study, driven by the data.

The first patient in the study was dosed on January 31, 2024. Since then, the study has completed Part 1 by progressing through the following dose levels: dose level 1 (125 mg of RVU120 and 200 mg of venetoclax), dose level 2 (200 mg and 200 mg respectively) and dose level 3 (250 mg and 400 mg respectively). RVU120 has demonstrated a consistent safety profile, with no new signals observed when combined with venetoclax at any dose level.

The Company has successfully completed Part 1 of the study and, based on the results, decided to advance it to Part 2, which is currently enrolling. Completion of Stage 1 enrollment for Part 2 (18 patients) is expected in Q1 2025.

The RIVER-81 study was initially launched at the clinical sites in Poland and Italy, followed by the activation of additional sites in Spain and France. As of December 11, 2024, all 33 sites planned for this year had been activated in these countries.

As of December 11, 2024, 28 patients were enrolled, with one patient (within eight patients treated with RVU120 at 250 mg (RP2D) that had at least one evaluable post-baseline assessment) achieving a CR and another achieving a blast reduction to a level below 5%.

RIVER-52: Phase II study of RVU120 as a single agent for the treatment of patients with genetically defined subtypes of AML (including NPM1 and DNMT3A mutations) and HR-MDS who have no alternative treatment options (NCT06268574).

The RIVER-52 study is a multicenter, open-label clinical trial designed to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD).

The study is divided into two parts. Part 1 aims to assess the level of anti-tumor activity in patients with genetically defined subtypes of AML, including NPM1 and DNMT3A mutations, as well as in patients with HR-MDS. Based on the outcomes of Part 1, Part 2 will further evaluate the safety, tolerability, and anti-tumor activity in a larger group of patients within the subtypes that exhibit the highest sensitivity to RVU120. The planned overall enrollment is approximately 40 to 140 patients, depending on the decision on the final scope of the study, driven by the data.

The first patient in the study was dosed on February 14, 2024. The RIVER-52 study was initially launched at clinical sites in Poland and Italy. Starting in September 2024, the study expanded to Spain, France and Canada. As of December 11, 2024, 42 out of 44 sites planned for this year had been activated.

As of December 11, 2024, 31 patients were enrolled, including 24 patients in cohorts 2-4 (NPM1-mutated, DNMT3A-mutated, and HR-MDS, respectively). One of two evaluable patients in cohort 2 achieved 50% blast reduction, while disease stabilizations and reductions of peripheral blasts were observed in patients in cohort 3.

Enrollment in the study significantly accelerated in Q4 2024 and is expected to lead to key efficacy readouts in the coming months. Data from at least 10 patients in each cohorts 2-4 are expected in H1 2025.

POTAMI-61: Phase II study of RVU120 as a single agent and in combination with ruxolitinib (RUX) for the treatment of patients with myelofibrosis (MF) (NCT06397313).

The POTAMI-61 study is a multicenter, open-label Phase II study of RVU120, being explored as a single agent for the treatment of patients with primary or secondary MF previously treated with or ineligible for a JAK inhibitor, e.g., ruxolitinib, and in combination with ruxolitinib for patients with suboptimal response to JAK inhibitors. Key endpoints will include spleen volume reduction (SVR), total symptom score (TSS) improvement, and reduction of bone marrow fibrosis.

The study has been initiated based on RVU120’s clinical safety and efficacy data observed in the RIVER-51 (Phase Ib in AML/HR-MDS) study, as well as translational data in MF generated in cooperation with Prof. Raajit Rampal from Memorial Sloan Kettering Cancer Center in New York. In vivo data demonstrate the beneficial effects of CDK8 inhibition in improving symptoms of MF, i.e., splenomegaly, hepatomegaly, anemia, and thrombopenia. Importantly, disease modification properties of RVU120 were shown by the reduction of mutated allele burden. RVU120 can potentially become a novel therapeutic strategy in myeloproliferative neoplasms (MPNs), including MF.

The POTAMI-61 study consists of two parts. Part A of the study, with a planned enrollment of approximately 20 patients, will comprise two cohorts: 1) single-agent therapy with RVU120 in patients resistant or refractory to prior JAK inhibitor treatment or ineligible for JAK inhibitor treatment and 2) RVU120 in combination with RUX in patients who experience a suboptimal response to prior JAK inhibitor treatment. Depending on results from Part A, cohorts 1 and/or 2 could be expanded in Part B, which will further assess safety, tolerability, and antitumor activity in a larger cohort, totaling up to approximately 230 patients for both Part A and Part B combined. RVU120 could also be investigated in a frontline setting in cohort 3. Ryvu will initially proceed with the execution of Part A of the study, while the decision on the potential initiation of Part B will be based on the outcomes of Part A.

The first patient in the study was dosed on December 4, 2024, and five more patients were undergoing screening as of December 11, 2024. Part A of the study will initially enroll patients across clinical sites in Poland and Italy. If Ryvu decides to initiate Part B, the study will expand to include additional sites in the EU and non-EU countries, totaling approximately 50 clinical sites worldwide. As of December 11, 2024, 12 out of 17 sites planned for this year had been activated.

Initial efficacy data is expected in Q2 2025, based on a 12-week patient observation period.

REMARK: Phase II study of RVU120 as a single agent for the treatment of patients with lower-risk myelodysplastic syndromes (LR-MDS) (NCT06243458)

The REMARK study is a multicenter, open-label Phase II study of RVU120, conducted as an investigator-initiated trial with the European Myelodysplastic Neoplasms Cooperative Group (EMSCO), with Prof. Uwe Platzbecker serving as the Coordinating Principal Investigator (CPI).

REMARK has been initiated based on the clinical safety and efficacy data gathered so far, and strong preclinical and mechanistic rationale.

MDS pathogenesis is influenced by gene expression alterations that hinder the maturation of hematopoietic cells. RVU120 triggers erythroid gene expression programs orchestrated by STAT5 and GATA1 in aberrant stem cells from MDS patients. Importantly, RVU120’s activity does not lead to significant hematopoietic toxicity. As a result, RVU120 is a promising drug candidate for treating transfusion-dependent MDS patients.

In the REMARK study, the planned overall enrollment is approximately 40 patients who receive RVU120 for at least 8 complete cycles (24 weeks). The primary goal is to achieve hematologic improvement in the form of an erythroid response (HI-E), with secondary goals including independence from RBC transfusions, improvement in hemoglobin levels, quality of life, disease progression, and analysis of specific gene mutations.

The first patient in the study was dosed on September 19, 2024, and as of December 11, 2024, 18 patients were treated. Patient enrollment commenced across five countries: Poland, Germany, France, Spain and Italy. As of December 11, 2024, 19 out of a planned total of 24 sites were activated.

Initial efficacy data is expected in Q2 2025, based on a 16-week observation period.

NEXT STEPS AND UPCOMING NEWSFLOW

RVU120 Phase II data update in Q2 2025. Following the key efficacy data expected in H1 2025, Ryvu plans to update stakeholders on the clinical progress of RVU120 in Q2 2025.

On December 12, 2024 Intensity Therapeutics, Inc. ("Intensity" or "the Company") (Nasdaq: INTS), a late-stage clinical biotechnology company focused on the discovery and development of proprietary, novel immune-based intratumorally injected cancer therapies intended to kill tumors directly and increase immune system recognition of cancers, and The Swiss Group for Clinical Cancer Research SAKK ("SAKK"), a decentralized academic research institute that has been conducting clinical trials of cancer treatments in all major Swiss hospitals since 1965, reported that Andreas Mueller, M.D., Past-President of the Project Group Breast Cancer of SAKK and Head of the Breast Center at Kantonsspital Winterthur, Switzerland and a supporting coordinating investigator for the study presented in an evening poster session on December 11 the final data from Intensity’s INVINCIBLE-2 Study (NCT04781725), and an overview / update of the INVINCIBLE-4 Study (NCT06358573) at the San Antonio Breast Cancer Symposium being held December 10-13, at the Henry B. Gonzalez Convention Center in San Antonio, Texas (Press release, Intensity Therapeutics, DEC 12, 2024, View Source [SID1234649087]).

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The INVINCIBLE-4 Study is a randomized open-label, multicenter study to determine the clinical activity, safety, and tolerability of INT230-6 in patients with early-stage, operable Triple Negative Breast Cancer ("TNBC") who undergo standard of care neoadjuvant immunochemotherapy ("SOC") treatment and SOC alone. The primary endpoint is pathological complete response ("pCR") in the primary tumor and affected lymph nodes. Patients will be randomized one to one to receive a regimen of either two doses of INT230-6 followed by SOC, which consists of pembrolizumab, anthracyclines, carboplatin, cyclophosphamide, and paclitaxel (i.e. the Keynote-522 regimen), or the SOC alone. The study is recruiting and expected to enroll 54 patients.

"Women with aggressive forms of breast cancer, such as TNBC, are often counseled to undergo pre-surgical (neoadjuvant) systemic therapy in advance to reduce the risk of the disease returning. Having a pathological complete response, meaning the absence of live cancer at the time of surgery, has been shown to result in a lower risk of recurrence. When the tumor diameters are bigger than two centimeters, recurrence is more likely, so that neoadjuvant treatment is warranted" said Dr. Mueller. "If the immunological cancer cell death caused by INT230-6 and the ignition of an anti-cancer immune response without increased toxicity shows a meaningful increase in pCR, it would be a major advance for the neoadjuvant treatment of breast cancer and potentially other cancers. Further, if the results of this study are highly favorable, perhaps the cardiotoxic anthracycline drugs could be reduced or eliminated in future studies."

The Company’s completed INVINCIBLE-2 Study, where INT230-6 was given alone in multiple tumor types including TNBC, showed several benefits:

Tumor-killing properties at levels greater than 95% in some patients on a single intratumoral dose with systemic immune activation.
Results in tumors larger than 2 cm showed significant necrosis in 74% of subjects at the time of surgery.
Gene expression analysis showed a significant difference between baseline biopsies and surgical specimens. Pathway analysis identified genes associated with TCR signaling, B-cell and T-cell activation, with increasing effects in post-treatment samples (SABCS 2023 #PS16-03).
The study demonstrated pathologic and immune priming effects of intratumoral cytotoxicity in traditional immune quiescent breast cancers, with a treatment that showed favorable safety and was well tolerated.
INT230-6 patients had significant differential gene expression present and identified genes were associated with T cell activation, lymphocyte activation and inflammatory response.
INT230-6 patients had increases in CD4 T cells and NK cells within the tumor, and associated changes in the diversity of T cell repertoire.
About INT230-6
INT230-6, Intensity’s lead proprietary investigational product candidate, is designed for direct intratumoral injection. INT230-6 was discovered using Intensity’s proprietary DfuseRx℠ technology platform. The drug is comprised of two proven, potent anti-cancer agents, cisplatin and vinblastine sulfate, and a penetration enhancer molecule (SHAO) that helps disperse potent cytotoxic drugs throughout tumors for diffusion into cancer cells. These agents remain in the tumor, resulting in a favorable safety profile. In addition to local disease control and direct tumor killing, INT230-6 causes a release of a bolus of neoantigens specific to the malignancy, leading to immune system engagement and systemic anti-tumor effects. Importantly, these effects are mediated without immunosuppression, which often occurs with systemic chemotherapy.

On December 12, 2024 RemeGen Co. Ltd. ("RemeGen") (9995.HK, 688331.SH) at the Poster Spotlight Session "Novel HER2 Therapeutics" of the 47th San Antonio Breast Cancer Symposium (SABCS), reported for the first time the data from a phase III study (RC48-C006, NCT03500380) of Disitamab Vedotin (DV) in treating patients with HER2-positive advanced breast cancer with liver metastasis (BCLM) (Press release, RemeGen, DEC 12, 2024, View Source [SID1234649086]). This is the first prospective randomized phase III study globally on a HER2-targeting ADC that demonstrated significant efficacy in patients with HER2-positive advanced BCLM. Professor Jiayu Wang from the Cancer Hospital, Chinese Academy of Medical Sciences presented and discussed the study. SABCS is one of the largest and most influential annual conferences focusing on advances in breast cancer clinical research, and this RemeGen sponsored study attracted the attention of experts worldwide.

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Data shows that about 45% of patients with HER2-positive advanced breast cancer have liver metastasis. This subset has a poor prognosis with a 5-year survival rate of only 8% to 12%, for whom no satisfactory therapies are available now.

This is a randomized, open-label, multicenter phase III study comparing the efficacy and safety of DV versus Lapatinib plus Capecitabine in patients with HER2-positive advanced BCLM. A total of 104 patients were enrolled, of whom 53 received DV and 50 received Lapatinib plus Capecitabine. All patients had previously been treated with Trastuzumab and Taxanes.

As of data cutoff date (December 31, 2023), according to the assessment by the Independent Review Committee (IRC), DV significantly improved progression-free survival (PFS) versus Lapatinib plus Capecitabine (median: 9.9 months vs. 4.9 months; hazard ratio [HR]: 0.56 [95% CI: 0.35-0.90]), which is consistent with the investigator-assessed PFS (HR: 0.62 [95% CI: 0.39-0.98]). The overall survival (OS) data, though immature, indicated a benefit trend in favor of DV. The safety profile was consistent with past DV use experience, with no new safety signals detected.

"This is the first confirmatory phase III study that demonstrated promising efficacy of an HER2-targeting ADC in patients with HER2-positive advanced BCLM," observed Professor Jiayu Wang. DV demonstrated clinically meaningful benefit compared with Lapatinib plus Capecitabine and a manageable safety profile, potentially offering a promising new treatment option for patients with HER2-positive advanced BCLM previously treated with Trastuzumab and Taxanes. The Biologics License Application (BLA) filing for this indication of DV has been accepted by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration in October 2024 and priority review was granted based on the breakthrough therapy designation.

On December 12, 2024 Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a global clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, reported late-breaking presentation of preclinical study results of novel humanized LIV-1 antibody based ADCs at 2024 San Antonio Breast Cancer Symposium (SABCS) (Press release, Transcenta, DEC 12, 2024, View Source [SID1234649085]). The ADCs (ADC-1 and ADC-2) were engineered using Transcenta’s proprietary antibody with site-specifical conjugation of Topoisomerase I Inhibitor payloads and these ADCs demonstrated significantly higher tumor regression activities than MMAE based ADCs in triple-negative breast cancer (TNBC) tumor models.

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Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, the responses are typically short lived. Thus, there is an urgent need to develop more effective treatments [1].

LIV-1, a member of the zinc transporter family and an estrogen-regulated gene in metastatic breast cancer, is overexpressed in a high prevalence in breast cancer (93%), including both TNBC and hormone receptor positive breast cancer, as well as in melanoma (82%), prostate (72%), ovarian (48%) and uterine (30%) cancer. This makes LIV-1 an attractive cell surface target for developing ADC therapeutics.

To develop next generation LIV-1 targeting ADC, Transcenta generated a proprietary novel humanized anti-LIV-1 mAb, 48D6, which displayed unique epitope form benchmark antibody, high binding affinity, specificity, excellent internalization ability. The conjugation method also eliminated FcR binding which resulted in significantly reduced non-specific FcR mediated binding and clearance, and improved pharmacokinetics profile in mice.

In vitro studies indicated that breast tumor cells, such as MDA-MB-468 and MCF-7, are more sensitive to Topo I inhibitor than MMAE. Consequently, Transcenta developed two Topo I inhibitor-based ADCs (ADC-1 and ADC-2) using glycotransferase mediated site-specific conjugation. Both ADC-1 and ADC-2 have a drug-to-antibody ratio (DAR) of 4 but with two different Topo I inhibitor payloads. A MMAE based ADC (ADC-3) with the same site-specific conjugation and DAR4 was also synthesized as the control.

Although ADC-1 and ADC-2 displayed similar and specific cytotoxic activities against human LIV-1-expressing tumor cells in vitro, as compared to SGN-LIV1A analog (DAR4) or ADC-3, they exhibited much higher maximal tumor cell killing than SGN-LIV1A analog in vivo. In addition, both ADC-1 and ADC-2 demonstrated a strong bystander effect which is important to overcome tumor heterogeneity.

In vivo pharmacology study revealed that ADC-1 or ADC-2 exhibited dose-dependent and more potent anti-tumor activities than the SGN-LIV1A analog or ADC-3 in the human LIV-1 transfected MDA-MB-468, a TNBC tumor model.

At 3 mg/kg the tumor growth inhibition (TGI)% were: ADC-1 92.4%, ADC-2 94.7%, ADC-3 68.5% and SGN-LIV1A analog 57.0% on Day 30. However, the overall response rate (ORR, 50% reduction of tumor volume from baseline) at 3mg/kg for SGN-LIV1A analog or ADC-3 was 0%, while ORRs of ADC-1 and ADC-2 were 40% and 70%, respectively. At 6 mg/kg, on Day 42, ORRs of ADC-1 and ADC-2 were 90% and 100%, respectively, and complete response (CR) rates were 90% and 100% respectively. The body weight of mice didn’t change significantly at either 3 or 6 mg/kg for ADC-1 or ADC-2.

"The significantly enhanced anti-tumor activities of ADC-1 and ADC-2 are likely due to the high affinity binding of 48D6 to LIV-1 and the high cytotoxicity of Topo I inhibitor for breast tumor cells." said Dr. Xueming Qian, Chairman of the Board and CEO at Transcenta, "These data warrant further investigation of the lead LIV-1 targeting ADCs (ADC-1 and ADC-2) as potential next-generation therapeutic agent in LIV-1 positive breast cancer and other solid tumors."

The 47th San Antonio Breast Cancer Symposium (SABCS) held from December 10 to 13, 2024, in San Antonio, Texas, USA. This Symposium is designed to provide state-of-the-art information on the experimental biology, etiology, prevention, diagnosis, and therapy of breast cancer and premalignant breast disease to an international audience of academic and private physicians and researchers.

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.