On December 9, 2022 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported continued robust long-term responses from its CART-ddBCMA Phase 1 expansion trial in patients with relapsed or refractory multiple myeloma, dosing of first patients in its iMMagine-1 Phase 2 clinical trial with pivotal drug product, and the initiation of the Phase 1 clinical trial of ACLX-002 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

38 patients were evaluable for efficacy and safety analysis as of the October 31, 2022 cutoff date, based on follow-up of at least one month, following treatment. These evaluable patients comprised the dose escalation cohorts for the first dose level (100 (+/- 20) million CAR+ T cells, n=6) and the second dose level (300 (+/- 20) million CAR+ T cells, n=6), and a dose expansion cohort at 100 (+/- 20) million CAR+ T cells (n=26). The median dose administered to patients in the first dose level and dose expansion cohorts was 115 million CAR+ T cells. All patients evaluable for this analysis have poor prognostic factors with 38 of 38 (100%) patients triple-refractory, 26 of 38 (68%) penta-refractory, and 22 of 38 (58%) with at least one high-risk prognostic factor (extramedullary disease (EMD), ISS Stage 3 [beta-2-microglobulin ≥5.5], bone marrow plasma cells (BMPC) ≥60%). All 38 patients had at least 3 prior lines of therapy.

The interim CART-ddBCMA Phase 1 clinical results (October 31, 2022 cutoff date) demonstrate deep and durable responses in patients with poor prognostic factors. Based on these data, the recommended Phase 2 dose (RP2D) was selected to be 115 (+/- 10) million CAR+T cells.

All Patients:

Of the 38 evaluable patients with median follow-up of 15 months

•
100% overall response rate (ORR) achieved in all patients per International Myeloma Working Group criteria

•
27 of 38 (71%) evaluable patients achieved complete response (CR) or a stringent complete response (sCR)

•
7 of 38 (18%) patients achieved very good partial response (VGPR)

•
4 of 38 (11%) patients achieved a partial response (PR)

•
34 of 38 (89%) patients achieved > VGPR

•
22 of 38 (58%) had high risk features (EMD, ISS stage 3, and/or BMPC ≥60%)

•
13 of 38 (34%) patients have extramedullary disease

Patients dosed 12 months prior or had their 12-month follow-up visit by November 22, 2022:

•
25 of 25 (100%) ORR

•
20 of 25 (80%) CR/sCR

•
3 of 25 (12%) VGPR

•
2 of 25 (8%) PR

•
23 of 25 (92%) > VGPR

Patients dosed 18 months prior or had their 18-month follow-up visit by November 22, 2022:

•
16 of 16 (100%) ORR

•
13 of 16 (81%) CR/sCR

•
1 of 16 (6%) VGPR

•
2 of 16 (13%) PR

•
14 of 16 (88%) > VGPR

CART-ddBCMA dosed at RP2D (115 million (+/- 10) CAR+ T cells) continues to be well-tolerated:

•
No tissue-targeted toxicities observed

•
No cases of delayed neurotoxicity events or parkinsonian symptoms

•
No cases of grade 3 (or greater) CRS and only one case (3%) of grade 3 ICANS event with no additional cases from previously reported

•
Based on the observed safety and efficacy of CART-ddBCMA, a dose of 115 (+/- 10) million CAR+ T cells was selected as the recommended phase 2 dose (RP2D)

Matthew J. Frigault, M.D., CART-ddBCMA study investigator and Assistant Director of the Cellular Therapy Service at Mass General Cancer Center and Instructor at Harvard Medical School said, "CART-ddBCMA continues to demonstrate deep responses. It is encouraging to see these clinical results with an autologous cell therapy, particularly in a population with high-risk features. Accessibility to treat multiple myeloma patients with CAR-T therapy remains an issue."

Arcellx’s Chairman and Chief Executive Officer, Rami Elghandour continued, "We’re excited by these long-term data as they are indicative of the potential for CART-ddBCMA to make a meaningful impact for patients and the physicians who need available therapies to treat them. These results supported the initiation of our iMMagine-1 Phase 2 pivotal trial where we recently dosed the first patients in this study. We look forward to completing enrollment of iMMagine-1 and advancing towards a BLA filing. Additionally, we are excited to have initiated our Phase 1 clinical trial for ACLX-002 utilizing our ARC-SparX platform for the treatment of patients with AML or MDS. Given the heterogeneity of these diseases, we believe that by leveraging the controllability and adaptability of ARC-SparX we can overcome a degree of the toxicity issues observed with traditional single antigen CAR-T therapies."

Presentation Details:

Title: Phase 1 Study of CART-ddBCMA for the Treatment of Subjects with Relapsed and/or Refractory Multiple Myeloma

Speaker: Matthew J. Frigault, M.D., Assistant Director of the Cellular Therapy Service at Mass General Cancer Center, and Instructor at Harvard Medical School

Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II

Session Date: Sunday, December 11, 2022

Session Time: 6:00 – 8:00 p.m. CT

Location: Ernest N. Morial Convention Center, Hall D, New Orleans, LA Publication Number: 3313

The presentation can be accessed on the company’s corporate website here.

Webcast Event:

Arcellx will host a live webcast event with an expert panel of clinicians to discuss the clinical results on Sunday, December 11, 2022, at 11:00 a.m. CT. The event will be accessible from Arcellx’s website at www.arcellx.com in the Investors section. A replay of the webcast will be archived and available for 30 days following the event.

About Multiple Myeloma

Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. Multiple myeloma is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.

About CART-ddBCMA

CART-ddBCMA is Arcellx’s BCMA-specific CAR-modified T-cell therapy utilizing the company’s novel BCMA-targeting binding domain for the treatment of patients with relapsed or refractory multiple myeloma. CART-ddBCMA is currently in a Phase 2 study. Arcellx’s proprietary binding domains are novel synthetic proteins designed to bind specific therapeutic targets. CART-ddBCMA has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

About iMMagine-1

iMMagine-1 is a Phase 2 pivotal, open-label, multicenter clinical trial designed to evaluate CART-ddBCMA, a BCMA-specific CAR-modified T-Cell therapy utilizing Arcellx’s novel BCMA-targeted binding domain, for the treatment of adult patients with relapsed or refractory multiple myeloma. The primary objective of this study is to evaluate the overall response rate over a 24-month period. In addition to safety, secondary endpoints include depth of disease response, duration of response, and overall survival over a 24-month period.

About AML

Acute myeloid leukemia (AML), also referred to as acute myelogenous leukemia, arises from cells in the bone marrow that have accumulated genetic mutations that cause the mutated cells to grow uncontrollably and disrupt the development of healthy blood cells. The aggressive growth of AML in the bone marrow and blood and the lack of durable treatments leave AML patients with an ~30% five-year survival rate. The disease is the most common acute leukemia affecting adults. According to the National Cancer Institute SEER database, there were an estimated 69,700 people living with AML in the United States in 2019. In 2022, new cases were estimated at approximately 20,050, with 11,540 deaths. Current therapies for AML have many limitations including limited efficacy and, in some cases, significant toxicities, highlighting the critical need to develop new therapies with greater safety and efficacy.

About MDS

Myelodysplastic syndrome (MDS) is a closely related disease to AML in which a population of abnormal myeloid cells develop in and disrupt the bone marrow. Depending on the type of abnormal or dysplastic cell that emerges, patients may experience a specific decrease in red blood cells or in the disease-fighting cell population referred to as monocytes, neutrophils, and dendritic cells. While MDS is itself a type of cancer, about one-third of MDS patients will also subsequently become diagnosed with AML. MDS is more common in elderly patients often diagnosed in their 70s but can also occur in non-elderly patients. MDS has been estimated to be as low as 10,000 new cases per year in the United States. While stem cell transplant can cure MDS, most patients are not able to receive them due to the typical advanced age at time of disease onset and the presence of co-morbidities, resulting in new therapies being needed for MDS patients as well.

About the ARC-SparX Platform Technology

The ARC-SparX platform is designed to allow for controllability and adaptability to potentially reduce toxicities that are often associated with serious dose-limiting adverse events and to overcome tumor heterogeneity. It is a modular therapy which utilizes a universal autologous ARC-T cell combined with one or more antigen-specific SparX protein to separate the tumor-recognition and tumor-killing functions. SparX (soluble protein antigen-receptor X-linkers) proteins utilize our D-Domain technology engineered to recognize antigens on the surface of diseased cells and flags those cells for detection by the ARC-T cells. ARC-T cells express a D-Domain-based CAR engineered to specifically recognize a unique TAG sequence in the SparX protein. ARC-T cells can be dosed separately and are designed to be activated to kill the target cell only when they encounter a SparX protein bound to the target antigen and thus can be controlled through dose modulation of the SparX protein. Arcellx has developed a collection of SparX proteins that bind different antigens on the surface of diseased cells. Multiple SparX proteins with different antigen specificity can be administered to potentially address antigen heterogeneity or antigen escape that contribute to relapsed and refractory disease.

About the Phase 1 Study Evaluating ACLX-002 for Patients with Acute Myeloid Leukemia or Myelodysplastic Syndrome (NCT05457010)

The Phase 1 study evaluating ACLX-002 in adults with relapsed and/or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) is an open-label, multicenter, dose escalation clinical trial designed to evaluate the safety of ACLX-002. Secondary objectives are to measure anti-tumor activity and pharmacokinetics of both SparX-002 and ARC-T cells.

On December 9, 2022 Arcellx, Inc. (NASDAQ: ACLX) and Kite, a Gilead Company (NASDAQ: GILD), reported a global strategic collaboration to co-develop and co-commercialize Arcellx’s lead late-stage product candidate, CART-ddBCMA, for the treatment of patients with relapsed or refractory multiple myeloma (Press release, Arcellx, DEC 9, 2022, View Source [SID1234624985]). Multiple myeloma is an incurable disease for most patients and the need remains for effective, safe, and broadly accessible therapies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This collaboration marks a significant achievement for the myeloma field and Arcellx," said Rami Elghandour, Arcellx’s Chairman and Chief Executive Officer. "Combining our potentially best-in-class CART-ddBCMA therapy for multiple myeloma with Kite’s global leadership in cell therapy provides the foundation for us to commercialize our therapy at scale. Most importantly this collaboration is focused on accelerating access for patients in need. The synergies between the two companies are a natural fit. We both bring complementary expertise to the collaboration allowing each company to contribute to the partnership without duplication or competing interests, which is critical for building long-term value."

Currently in Phase 2 clinical development, CART-ddBCMA is an investigational cell therapy product comprising autologous T cells that have been genetically modified to target multiple myeloma. CART-ddBCMA utilizes Arcellx’s novel D-Domain binder. Kite and Arcellx will jointly advance the CART-ddBMCA asset.

"The collaboration with Arcellx enables Kite to expand into a new area of high unmet need and bring a potentially best-in-class cell therapy to help many patients," said Christi Shaw, Chief Executive Officer of Kite. "Cell therapy has proven it can change the way cancer is treated by creating a potentially curative therapy for an individual patient, engineered from their own T cells. To deliver cell therapy globally, and at scale, it requires a highly coordinated, vertically integrated organization from R&D to commercialization to manufacturing, dedicated to the unique needs of this very complex field. The Kite team is excited to engage on this meaningful program in the multiple myeloma field, alongside Arcellx’s talented team."

Upon closing, Arcellx will receive an upfront cash payment of $225 million and $100 million equity investment. Both companies will share development, clinical trial, and commercialization costs for CART-ddBCMA and will jointly commercialize and split U.S. profits 50/50. Outside the US, Kite will commercialize the product and Arcellx will receive royalties on sales. Kite will be responsible for the development and commercialization costs for any product under the collaboration that is not co-commercialized. After completion of the technical transfer, Kite will be responsible for manufacturing.

Terms of the Collaboration

Upfront: Upon closing, Arcellx will receive an upfront cash payment of $225 million and $100 million equity investment from Kite.

Manufacturing: After completion of the technical transfer, Kite will be responsible for manufacturing. Kite will be responsible for all manufacturing expenses associated with commercial readiness.

Development: U.S. and global study costs for the iMMagine-1, iMMagine-2 and future clinical studies for CART-ddBCMA and any other co-commercialized product will be shared 50/50 in the U.S. and 60 to Kite / 40 to Arcellx in the Ex U.S. territory.

U.S. Commercialization: 50/50 profit split for products co-commercialized by Arcellx and Kite; Kite will commercialize all other products and Arcellx will receive low to mid teen royalties.

Ex-U.S. Commercialization: Kite will commercialize the product and Arcellx will receive low to mid-teen royalties on sales.

NextGen, Non-Autologous, and ARC-SparX Programs: Arcellx and Kite to collaborate on next generation autologous and non-autologous programs incorporating ddBCMA. Arcellx to receive an option to co-develop and co-commercialize next generation autologous programs and Kite to receive an option to selected ARC-SparX programs in myeloma.

Bank of America is acting as financial advisor to Kite. Wilson Sonsini Goodrich & Rosati is serving as legal counsel to Arcellx.

The transaction is expected to close in the first quarter of 2023. Closing of the transaction is subject to expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions.

Conference Call and Webcast Details

The live webcast and conference call will be accessible under the Events & Presentations in the Investors section of the company’s website www.arcellx.com. To participate in the conference call, dial 1-888-440-3310 (domestic) or 1-646-960-0513 (international) and reference conference ID# 1012518. The archived audio webcast will be available on Arcellx’s website following the call and will be available for 30 days.

About Multiple Myeloma

Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. Multiple myeloma is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.

About CART-ddBCMA

CART-ddBCMA is Arcellx’s BCMA-specific CAR-modified T-cell therapy utilizing the company’s novel binding domain for the treatment of patients with relapsed or refractory multiple myeloma. CART-ddBCMA is currently being investigated in a pivotal Phase 2 study called iMMagine-1. Arcellx’s proprietary binding domains are novel synthetic proteins designed to bind specific therapeutic targets. CART-ddBCMA has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

On December 9, 2022 Imugene Limited (ASX:IMU), a clinical stage immuno-oncology company, reported new and first data from triple negative breast cancer (TNBC) patients in the Phase I CHECKVacc trial has been presented as a poster presentation at the 2022 San Antonio Breast Cancer Symposium (SABC 2022) on 9 December 2022 AEDT in San Antonio, Texas (Press release, Imugene, DEC 9, 2022, View Source [SID1234624966]). Information is also available on the company’s website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The presentation, titled "Phase I study of intratumoral administration of CF33-hNIS-antiPD-L1 (CHECKvacc) in patients with metastatic triple negative breast cancer", was presented by Dr Yuan Yuan M.D., PhD, Cedars Sinai Medicine, Los Angeles and Dr Jamie Rand M.D., City of Hope, Los Angeles.

Imugene MD & CEO Leslie Chong said: "Phase 1 trials are generally designed to look for safety, tolerability and early response signals to determine the optimal dose for further development. I am encouraged that we are seeing positive signals with correlative biomarker and imaging data at such an early stage of our CHECKVacc Phase I trial."

CF33-hNIS-antiPD-L1 administered by intratumoral injection in patients with metatstatic TNBC is safe and well tolerated at the dose levels tested.

Highlights and results include:

1. From October 2021 to June 2022, 6 patients were enrolled in this ongoing study and received at least 1 dose of CHECKvacc injection at dose level 1 (1 x 10^5 pfu) or dose level

2 (3 x 10^5 pfu). 2. No dose-limiting toxicities were observed. No treatment related adverse events were reported for 6 patients except 1 patient with injection site discoloration.

3. 99mTc SPECT imaging for virus tracking from virus induced replication of the human sodium iodide (hNIS) transgene shows enhancement in 4/6 (67%) patients in the first 2 dose levels. Enhancement was greater in patients with injection of nodal disease compared to dermal metastasis.

4. SPECT imaging of patient COH-004 (DL-2) on C1D8 showed significant enhancement of injected lymph node.

5. Baseline and on-treatment tumor biopsies of patient COH-004 using spatial immune profiling showed an increase in PD-L1 positive cells following treatment with CHECKVacc, demonstrating immune activation and tumor microenvironment changes in association with response to therapy. IMUGENE LIMITED ACN 009 179 551 2

Taken together, these data support further evaluation of CHECKVacc in TNBC. CF33-hNIS-antiPDL1 is an immune checkpoint inhibitor armed chimeric vaccinia poxvirus from the lab of CF33 inventor Professor Yuman Fong, Chair of Sangiacomo Family Chair in Surgical Oncology at City of Hope, one of the largest cancer research and treatment organizations in the United States, and a noted expert in the oncolytic virus field.

Oncolytic viruses (OVs) are designed to both selectively kill tumour cells and activate the immune system against cancer cells, with the potential to improve clinical response and survival.

Full study details can also be found on clinicaltrials.gov under study ID: NCT05081492

On December 8, 2022 Replimune Group, Inc. (Nasdaq: REPL), a clinical stage biotechnology company pioneering the development of a novel class of tumor-directed oncolytic immunotherapies, reported the pricing of its public offering of 5,374,486 shares of its common stock at a public offering price of $23.50 per share (Press release, Replimune, DEC 9, 2022, View Source [SID1234624958]). In addition, in lieu of common stock to certain investors, Replimune reported the pricing of its public offering of pre-funded warrants to purchase 4,200,000 shares of its common stock at a purchase price of $23.4999 per pre-funded warrant, which equals the public offering price per share of the common stock less the $0.0001 per share exercise price of each pre-funded warrant. The aggregate gross proceeds from the offering are expected to be approximately $225 million, before deducting the underwriting discounts and commissions and offering expenses payable by Replimune. All securities in the offering are being offered by Replimune. In addition, Replimune has granted the underwriters a 30-day option to purchase up to an additional 1,436,172 shares of its common stock from Replimune at the public offering price, less the underwriting discounts and commissions. The offering is expected to close on December 13, 2022, subject to the satisfaction of customary closing conditions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

J.P. Morgan Securities LLC, SVB Securities LLC, Piper Sandler and BMO Capital Markets Corp. are acting as joint book-running managers for the offering.

A preliminary prospectus supplement relating to and describing the terms of the offering were filed with the Securities and Exchange Commission (the "SEC") on December 7, 2022. The final prospectus supplement relating to the offering will be filed with the SEC. Copies of the final prospectus supplement and the accompanying prospectus relating to the offering may be obtained, when available, by visiting EDGAR on the SEC website at www.sec.gov or from J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204, or by e-mail at [email protected]; SVB Securities LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at 1-800-808-7525, ext. 6105, or by email at [email protected]; Piper Sandler, Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, by telephone at (800) 747-3924, or by email at [email protected]; BMO Capital Markets Corp., Attention: Equity Syndicate Department, 151 W 42nd Street, 32nd Floor, New York, NY 10036, by telephone at (800) 414-3627, or by email at [email protected]. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the SEC.

The securities described above are being offered by Replimune pursuant to its shelf registration statement on Form S-3, including a base prospectus, that was previously filed by Replimune with the SEC on June 23, 2022 and declared effective by the SEC on July 27, 2022. This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of these securities, in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 8, 2022 iOnctura SA a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways, reported the first patient has been dosed in a Phase Ib clinical trial of IOA-289 in metastatic pancreatic cancer (Press release, iOnctura, DEC 8, 2022, View Source [SID1234640235]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to progress clinical development of our autotaxin (ATX) inhibitor IOA-289, the second most advanced product in our pipeline," said Catherine Pickering, PhD, CEO of iOnctura. "Our preclinical research has uncovered a central role for ATX as a tumor survival factor, especially in highly fibrotic malignancies such as pancreatic, liver, colorectal, ovarian and breast cancers. To our knowledge, this is the first time an ATX inhibitor will be investigated in cancer patients. The learnings from this study will serve as a prototype to explore the therapeutic potential of IOA-289 in further fibrotic cancers."

The Phase Ib AION-02 study (NCT05586516) is a dose-escalation study of IOA-289 in combination with standard-of-care gemcitabine/nab-paclitaxel chemotherapy in first-line metastatic pancreatic cancer. Patients will be dosed with IOA-289 monotherapy for 7 days before commencing combination treatment of IOA-289 and chemotherapy.

Fibrotic cancers, including pancreatic cancer, are characterized by the deposition of thick layers of extracellular matrix containing collagen fibers and pro-tumorigenic factors. This microenvironment impedes the entry of immune cells and drugs, making the tumors difficult to treat.

"IOA-289 is an orally dosed small molecule that has been shown preclinically to have a multi-pronged approach to treating cancer, acting directly to prevent proliferation of tumor cells and indirectly to potentiate the actions of the immune system and chemotherapy in the fibrotic microenvironment." said David Brindley, Professor of Biochemistry, University of Alberta, and member of iOnctura’s clinical advisory board. "We hypothesize that the lead-in of IOA-289 will reduce the expression of collagen and other pro-tumorigenic secreted factors rendering the tumor microenvironment susceptible to chemotherapy and unveiling the tumor to the immune system."

The trial’s primary endpoint is to evaluate the safety and tolerability of the ascending doses of IOA-289. Secondary endpoints include biomarker changes and efficacy endpoints. The trial will be conducted in sites in Italy and the UK. The principal investigators of the trial are Professor Davide Melisi, University of Verona, Professor Michele Maio, University of Siena and Professor Jeff Evans, University of Glasgow.

IOA-289 is the first autotaxin (ATX) inhibitor in clinical development for cancer. It is an oral small molecule non-competitive inhibitor with novel binding chemistry and a safe clinical profile. It has been shown that inhibiting ATX with IOA-289 directly prevents the proliferation of cancer cells1. Furthermore, IOA-289 interrupts resistance to cancer therapy by reducing fibrotic scar tissue, unveiling the tumor and enabling the immune system to recruit infiltrating lymphocytes into the tumor2. Thanks to this multi-pronged mode of attack, IOA-289 reduced tumor burden in mouse pancreatic cancer models1.

Pancreatic cancer (PDAC): Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer accounting for approximately 90% of cases. PDAC has a poor prognosis, with less than 5% of patients surviving beyond five years after diagnosis. There are over 50,000 diagnoses of pancreatic cancer each year in the United States and over 65,000 in the EU5.