On November 7, 2024 Cullinan Therapeutics, Inc. (Nasdaq: CGEM; "Cullinan"), a biopharmaceutical company focused on developing modality-agnostic targeted therapies, reported recent and anticipated business highlights and announced its financial results for the third quarter ended September 30, 2024 (Press release, Cullinan Oncology, NOV 7, 2024, View Source [SID1234647926]).

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 making meaningful progress in executing our strategic plans for CLN-978 in autoimmune diseases while simultaneously advancing our oncology pipeline," said Nadim Ahmed, Chief Executive Officer of Cullinan Therapeutics. "We have secured clearance from the U.S. Food and Drug Administration (FDA) for our IND application and Human Research Ethics Committee (HREC) approval in Australia to initiate our global Phase 1 study for CLN-978 in moderate to severe SLE. These important regulatory clearances position us to share initial clinical data for CLN-978 in the fourth quarter of 2025. We also continue to make significant progress in advancing our oncology portfolio, with data from two of our key programs expected in 2025. For CLN-619, we remain on track to share initial expansion data for endometrial and cervical cancers in the second quarter of 2025. We also completed enrollment of the pivotal Phase 2b study of zipalertinib ahead of schedule, and we plan to provide the results at mid-year 2025."

Portfolio Highlights

Immunology

•
CLN-978 (CD19xCD3 T cell engager): Systemic lupus erythematosus and rheumatoid arthritis
o
The company obtained health authority approvals to initiate its global Phase 1 study in moderate to severe SLE, securing U.S. FDA clearance of its IND application and HREC approval in Australia. Cullinan plans to share initial clinical data for SLE in the fourth quarter of 2025. The company also continues to engage with other global health authorities to expand the planned country and site footprint.
o
The company plans to initiate a sponsored clinical trial in rheumatoid arthritis (RA) in the second quarter of 2025. The trial will be designed and executed in collaboration with FAU Erlangen-Nuremberg in Germany and Università Cattolica del Sacro Cuore, Rome in Italy.
o
Cullinan is presenting preclinical data at the upcoming American College of Rheumatology (ACR) Convergence 2024, taking place in Washington, D.C. from November 14-19, 2024.
Oncology

•
CLN-619 (Anti-MICA/MICB monoclonal antibody):Solid tumors and hematological malignancies
o
In September, Cullinan dosed the first patient in a Phase 1 study of CLN-619 in patients with relapsed/refractory multiple myeloma.
o
New biomarker and translational data from the monotherapy dose escalation portion of the Phase 1 study in solid tumors will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in November.
o
The company continues enrollment of disease-specific expansion cohorts of its Phase 1 study in solid tumors, enrolling cervical, endometrial and non-small cell lung cancer (NSCLC) patients. Cullinan remains on track to report initial data in endometrial and cervical cancers in the second quarter of 2025.
o
Notably, the company was issued a key composition of matter patent by the United States Patent and Trademark Office, which is expected to extend protection until at least 2041, excluding possible patent term extension.

•
Zipalertinib (EGFR ex20ins inhibitor), collaboration with Taiho Oncology: EGFR ex20ins NSCLC
o
At the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September, Cullinan presented positive REZILIENT1 results in patients with EGFR ex20ins NSCLC who have progressed on or after prior amivantamab treatment. Zipalertinib demonstrated a consistent objective response rate of approximately 40% and a manageable safety profile.
o
In September, Cullinan successfully completed enrollment of the pivotal Phase 2b study ahead of schedule, which was originally planned for the end of this year. Cullinan plans to share the results of the pivotal Phase 2b study at mid-year 2025. Taiho continues enrollment of the pivotal study REZILIENT3 in 1L EGFR ex20ins NSCLC.
•
CLN-049 (FLT3xCD3 T cell-engaging bispecific antibody): AML and MDS
o
Following the clinical update in Q2 2024 and discontinuation of subcutaneous administration, enrollment continues with IV administration in the ongoing Phase 1 study in patients with relapsed/refractory AML and MDS.
•
CLN-617 (IL-2 and IL-12 cytokine fusion protein): Solid tumors
o
Enrollment continues in the ongoing Phase 1 study in patients with advanced solid tumors.
Corporate Updates

•
In the third quarter, the company added two rheumatology and immunology experts to its Scientific Advisory Board (SAB): Dr. Ricardo Grieshaber-Bouyer and Dr. Chaim Putterman. Dr. Grieshaber-Bouyer and Dr. Putterman’s expertise will further strengthen the company’s Scientific Advisory Board.
o
Dr. Grieshaber-Bouyer is head of the clinical trial unit at FAU Erlangen-Nurnberg Rheumatology and Immunology Department and cares for patients with rheumatic and immune-mediated diseases, in particular in the context of emerging therapies such as T cell redirecting therapies.
o
Dr. Putterman is Professor Emeritus of the Division of Rheumatology at Albert Einstein College of Medicine and Montefiore Medical Center, where his research focuses on mechanisms of autoimmunity, pathogenesis of kidney and neuropsychiatric disease in SLE, novel therapies for lupus, and SLE biomarkers.

Third Quarter 2024 Financial Results

•
Cash Position: Cash, cash equivalents, short- and long-term investments, and interest receivable were $639.0 million as of September 30, 2024. Cullinan continues to expect its cash resources to provide runway into 2028 based on its current operating plan.
•
R&D Expenses: Research and development expenses were $35.5 million for the third quarter of 2024, compared to $33.8 million for the same period in 2023.
•
G&A Expenses: General and administrative expenses were $13.3 million for the third quarter of 2024, compared to $11.0 million for the same period in 2023.
•
Net loss: Net loss was $40.6 million ($0.69 per common share) for the third quarter of 2024, compared to $39.2 million ($0.91 per common share) for the same period in 2023.

On November 7, 2024 Cidara Therapeutics, Inc. (Nasdaq: CDTX) (the Company), a biotechnology company using its proprietary Cloudbreak platform to develop drug-Fc conjugate (DFC) immunotherapies designed to save lives and improve the standard of care for patients facing serious diseases, reported financial results for the third quarter ended September 30, 2024, and provided an update on its corporate activities and product pipeline (Press release, Cidara Therapeutics, NOV 7, 2024, View Source [SID1234647924]).

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 recent initiation of our Phase 2b NAVIGATE clinical trial, which will evaluate the efficacy and safety of CD388 for the pre-exposure prophylaxis of seasonal influenza, represents an important clinical achievement for our company," said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara. "Additionally, the realignment of our organization will ensure the most efficient use of our resources, enabling us to focus on advancing our promising CD388 clinical program. Based on the compelling data generated to date, we believe CD388 has the potential to provide long-term protection against both seasonal and pandemic strains of influenza with a single dose per flu season."

Recent Corporate Highlights

Dosed first subjects in Phase 2b NAVIGATE trial evaluating efficacy and safety of CD388 for the pre-exposure prophylaxis of seasonal influenza. In September 2024, Cidara initiated a randomized, double-blind, controlled Phase 2b trial targeting enrollment of 5,000 healthy, unvaccinated adult subjects who are not at risk of complications from influenza. Three CD388 dose groups and one placebo group are being randomized in a 1:1:1:1 ratio and we administered CD388 at the beginning of this influenza season. Subjects will be followed for the remainder of the influenza season to monitor for breakthrough cases. Rates of laboratory and clinically confirmed influenza will be compared between subjects receiving the various single doses of CD388 or placebo. The study includes sites in the U.S. and UK.
Highlighted CD388 in two presentations at the 2024 IDWeek Conference. In October 2024, positive Phase 2a human challenge study data were presented in an oral presentation, which demonstrated that a single subcutaneous dose of CD388 administered five days prior to influenza challenge was shown to be effective in preventing symptomatic disease. Positive first-in-human data from a Phase 1 trial studying the safety and PK of CD388 administered by intramuscular and subcutaneous injection were also presented. The results showed that CD388 was rapidly absorbed to achieve target exposure levels and slowly eliminated, regardless of administration route, with no concerning safety signals, supporting the potential for a single dose of CD388 per flu season.
Highlighted CD388 in an oral and poster presentation at the 2024 OPTIONS XII for the Control of Influenza conference. Phase 1 and Phase 2a safety data from three clinical trials on the Company’s CD388 asset were presented in oral presentation format, and pharmacokinetics and safety of CD388 following subcutaneous administration in healthy Japanese participants were presented. Overall, results were consistent with a previous Phase 1 clinical study in Western participants. CD388 injection was well tolerated, and the data support further clinical studies with CD388 in the Japanese population for the prevention of seasonal influenza.
Strengthened Scientific Advisory Board (SAB) with four infectious disease experts. In September 2024, Rick Bright, Ph.D., Philip Krause, M.D., Mario Barro, Ph.D., and Frederick Hayden, M.D., FACP, were appointed to the Company’s SAB. The new members’ collective expertise working in infectious diseases including influenza, pandemic preparedness, and clinical and regulatory processes will be instrumental as Cidara conducts its CD388 Phase 2b NAVIGATE trial.
Appointed Jim Beitel as Chief Business Officer. In August 2024, Jim Beitel joined Cidara as Chief Business Officer. Mr. Beitel brings over 20 years of experience in life science corporate development, including strategy, business development, commercialization, finance, and other roles.
Restructured workforce to focus on planned clinical development of CD388. In September 2024, Cidara announced an approximate 30% reduction in workforce to focus on the clinical development of its novel DFC candidate for influenza A and B, CD388. This restructuring is expected to substantially reduce Cidara’s capital needs related to recurring personnel costs.
Third Quarter 2024 Financial Results

Cash and cash equivalents totaled $127.4 million as of September 30, 2024, compared with $35.8 million as of December 31, 2023.
Revenue was zero and $1.3 million for the three and nine months ended September 30, 2024, respectively, compared to $9.2 million and $20.5 million for the same periods in 2023, respectively. Revenue for the three and nine months ended September 30, 2024 and 2023 related to research and development and clinical supply services provided to J&J Innovative Medicine, previously Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), under our license and collaboration agreement with Janssen (the Janssen Collaboration Agreement). The Janssen Collaboration Agreement was terminated upon the effectiveness of our license and technology transfer agreement with Janssen (the Janssen License Agreement) on April 24, 2024.
Acquired in-process research and development expenses were $84.9 million for the nine months ended September 30, 2024 and related to an upfront payment of $85.0 million paid to Janssen under the Janssen License Agreement, on April 24, 2024, plus $0.4 million in direct transaction costs, offset by a settlement gain of $0.5 million to settle the preexisting Janssen Collaboration Agreement relationship.
Research and development expenses were $12.4 million and $25.0 million for the three and nine months ended September 30, 2024, respectively, compared to $10.4 million and $28.8 million for the same periods in 2023, respectively. The increase in research and development expenses for the three months ended September 30, 2024, compared to the three months ended September 30, 2023 is primarily due to higher expenses associated with our CD388 Phase 2b NAVIGATE study and higher personnel costs, including $1.2 million for severance payments and employee benefits related to a reduction in force, offset by lower nonclinical expenses associated with our Cloudbreak platform. The decrease in research and development expenses for the nine months ended September 30, 2024, compared to the nine months ended September 30, 2023 is primarily due to lower nonclinical expenses associated with our Cloudbreak platform, offset by higher expenses associated with our CD388 Phase 2b NAVIGATE study and higher personnel costs, including $1.2 million for severance payments and employee benefits related to a reduction in force.

Selling, general and administrative (SG&A) expenses were $5.0 million and $13.3 million for the three and nine months ended September 30, 2024, respectively, compared to $3.3 million and $10.1 million for the same periods in 2023, respectively. The SG&A expenses for all periods primarily relate to consulting, personnel and legal costs.
On April 24, 2024, Cidara entered into an asset purchase agreement with Napp Pharmaceutical Group Limited (Napp) an affiliate of Mundipharma Medical Company, pursuant to which we sold to Napp all of our rezafungin assets and related contracts. We completed all conditions of the sale on April 24, 2024. We determined that the sale of rezafungin represented a strategic shift that will have a major effect on our operations and financial results. Accordingly, the sale of rezafungin is classified as discontinued operations. We have separately reported the financial results of rezafungin as discontinued operations in the condensed consolidated statements of operations and comprehensive loss for all periods presented. Net loss from discontinued operations for the three months ended September 30, 2024, was $0.5 million and net income from discontinued operations for the nine months ended September 30, 2024 was $0.4 million, compared to net loss from discontinued operations of $5.3 million and $2.8 million for the same periods in 2023, respectively.

Net loss for the three and nine months ended September 30, 2024 was $16.0 million and $117.5 million, respectively, compared to a net loss of $9.1 million and $19.7 million for the same periods in 2023, respectively.
On July 18, 2024, the Company’s stockholders approved the issuance of up to 16,800,000 shares of common stock upon conversion of 240,000 shares of Series A Convertible Voting Preferred Stock issued in our private placement completed in April 2024. On July 19, 2024, the Company issued 2,469,250 shares of common stock upon automatic conversion of 35,275 shares of Series A Convertible Voting Preferred Stock.
During the three and nine months ended September 30, 2024, Cidara did not sell any shares of common stock pursuant to its at-the-market sales agreement.

As of September 30, 2024, Cidara had 7,046,633 shares of common stock outstanding, 204,725 shares of Series A Convertible Voting Preferred Stock outstanding, which are convertible into 14,330,750 shares of common stock, and 2,104,472 shares of Series X Convertible Preferred Stock outstanding, which are convertible into 1,052,236 shares of common stock, for a total of 22,429,619 shares of common stock equivalents outstanding.

On November 7, 2024 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, reported financial results and recent highlights for the third quarter ended September 30, 2024 (Press release, Cardiff Oncology, NOV 7, 2024, View Source [SID1234647923]).

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 quarter has been exciting as our Phase 2 clinical trial in second-line KRAS-mutant mCRC was published in one of the most esteemed medical journals in the field of oncology, Journal of Clinical Oncology. Our findings demonstrated that onvansertib combined with FOLFIRI/bev was well-tolerated, and revealed a 7.7x greater clinical benefit in bev naïve patients compared to patients who were previously treated with bev," said Mark Erlander, Ph.D., Chief Executive Officer of Cardiff Oncology. "We believe the results of our JCO publication validate our ongoing CRDF-004 trial evaluating onvansertib + chemo for the treatment of mCRC in the first-line setting, where all patients are bev naïve. Furthermore, we are pleased with the progress we have made in the trial as we leverage Pfizer’s resources and capabilities, and are grateful for the commitment from the patients and investigators at our trial sites across the U.S. As of today, the trial continues to generate patient data that will allow us to provide an initial data release by the end of the year. Overall, we are optimistic about onvansertib’s potential to become a meaningful treatment option for the 50,000 new patients diagnosed with RAS-mutated mCRC in the U.S. every year who have not had access to any new treatment options in several decades."

Upcoming expected milestones

•
First-line RAS-mutated metastatic colorectal cancer (mCRC) randomized initial data readout from the CRDF-004 trial expected by end of 2024

Company highlights for the quarter ended September 30, 2024 and subsequent weeks include:

•
Published clinical data of the combination of onvansertib with FOLFIRI and bev in second-line KRAS mutant mCRC in the peer-reviewed Journal of Clinical Oncology, the flagship publication of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)
•
Phase 2 clinical trial treating patients with KRAS-mutant mCRC (NCT03829410) demonstrated that onvansertib combined with FOLFIRI and bev was well-tolerated, and exhibited clinical activity in the second-line setting.
•
A post hoc analysis revealed a greater clinical benefit in bev naïve patients, who demonstrated an ORR of 77% and mPFS of 14.9 months compared to an ORR of 10% and mPFS of 6.6 months in those previously exposed to bev.

•
Published promising preclinical data demonstrating the combination of onvansertib and alpelisib in PIK3CA-mutated HR-positive breast cancer resistant to palbociclib and endocrine therapy in the peer-reviewed journal, Cancers
•
The combination of onvansertib and alpelisib synergistically inhibited cell viability, suppressed PI3K signaling, and induced G2/M arrest and apoptosis in PI3K-activated cell lines.
•
The combination demonstrated superior anti-tumor activity compared to the single agents in three PDX models.
•
Pharmacodynamic studies confirmed inhibition of both PLK1 and PI3K activity and pronounced apoptosis in the combination-treated tumors.
•
The findings support that targeting PLK1 and PI3Kα with onvansertib and alpelisib, respectively, may be a promising strategy for patients with PIK3CA-mutant HR+ breast cancer failing ET + CDK4/6i therapies and warrant clinical evaluation.
Third Quarter 2024 Financial Results

Liquidity, cash burn, and cash runway

As of September 30, 2024, Cardiff Oncology had approximately $57.7 million in cash, cash equivalents, and short-term investments.

Net cash used in operating activities for the third quarter of 2024 was approximately $10.5 million, an increase of approximately $2.5 million from $8.0 million for the same period in 2023.

Based on its current expectations and projections, the Company believes its current cash resources are sufficient to fund its operations into Q1 2026.

Operating results

Total operating expenses were approximately $12.8 million for the three months ended September 30, 2024, an increase of $1.8 million from $11.0 million for the same period in 2023. The increase in operating expenses was primarily due to clinical programs and outside service costs related to the development of our lead drug candidate, onvansertib.

On November 7, 2024 Boundless Bio (Nasdaq: BOLD), a clinical-stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported business updates and reported financial results for the third quarter of 2024 (Press release, Boundless Bio, NOV 7, 2024, View Source [SID1234647922]).

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 third quarter was marked by steady execution across the portfolio, with the POTENTIATE and STARMAP trials continuing to enroll patients," said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. "In September, together with our development partner, SOPHiA GENETICS, we presented analytical validation for our proprietary ecDNA diagnostic, ECHO, a critical first step in identifying ecDNA positive patients for our clinical programs. We are capitalized to advance our lead programs through proof-of-concept data and remain focused on delivering impactful results for our patients and stakeholders."

Program Highlights and Upcoming Milestones

BBI-355, a novel, oral, potent, selective CHK1 inhibitor targeting replication stress for cancer patients with driver oncogene amplifications

•
Enrollment is proceeding in the Phase 1/2 POTENTIATE clinical trial evaluating BBI-355 as a single agent and in combination with targeted therapies in patients with oncogene amplified solid tumors.
•
No new safety signals have been observed.
•
The company anticipates reporting initial clinical proof-of-concept data in the second half of 2025.

BBI-825, a novel, oral, potent, selective RNR inhibitor targeting ecDNA assembly and repair for cancer patients with resistance oncogene amplifications

•
Enrollment continues to progress in the single agent, dose-escalation portion of the STARMAP clinical trial, with initial clinical proof-of-concept data expected in the second half of 2025.

ecDTx 3, a novel kinesin program involved in ecDNA segregation

•
The company’s third ecDTx program, directed to a previously undrugged kinesin target essential for ecDNA segregation whose inhibition is synthetic lethal to ecDNA-enabled cancer cells, continues to advance through lead optimization.

ECHO, a proprietary diagnostic for detection of ecDNA amplified oncogenes

•
In September, analytical validation data was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress for the company’s proprietary ecDNA diagnostic ECHO (ecDNA Harboring Oncogenes). ECHO is currently being used as a clinical trial assay to determine ecDNA status of patients enrolled in the BBI-355 POTENTIATE trial.

Third Quarter 2024 Financial Results

•
Cash Position: Cash, cash equivalents, and short-term investments totaled $167.1 million as of September 30, 2024.
•
R&D Expenses: Research and development (R&D) expenses were $14.1 million for the third quarter of 2024 compared to $11.6 million for the same period in 2023.
•
G&A Expenses: General and administrative (G&A) expenses were $4.6 million for the third quarter of 2024 compared to $3.3 million for the same period in 2023.
•
Net Loss: Net loss totaled $16.5 million for the third quarter of 2024 compared to $13.2 million for the same period in 2023.

About BBI-355

Boundless Bio’s lead ecDNA-directed therapy (ecDTx), BBI-355, is a novel, oral, selective small molecule inhibitor of checkpoint kinase 1 (CHK1) being studied in the ongoing, first-in-human, Phase 1/2 POTENTIATE clinical trial (NCT05827614) in cancer patients with oncogene amplifications. CHK1 is a master regulator of cells’ response to replication stress (RS). RS is elevated in cancer cells with oncogene amplification, including on ecDNA, and, because of this, represents a key vulnerability of those cells. BBI-355 was designed to exploit the elevated RS in ecDNA-enabled oncogene amplified cancer cells by disrupting proper CHK1 function in regulating RS and thereby facilitating catastrophic RS to preferentially kill cancer cells relative to healthy cells.

About BBI-825

Boundless Bio’s second ecDTx, BBI-825, is a novel, oral, selective small molecule inhibitor of ribonucleotide reductase (RNR) being studied in the ongoing, first-in-human, Phase 1/2 STARMAP clinical trial (NCT06299761) in colorectal cancer patients with BRAFV600E or KRASG12C mutations and resistance gene amplifications. In preclinical studies, BBI-825 demonstrated low double digit nanomolar RNR inhibition and tumor growth inhibition, including regressions, in both the prevention and treatment of amplification-mediated resistance in mitogen-activated protein kinase (MAPK) pathway-activated tumors. RNR is the rate-limiting enzyme responsible for cellular de novo synthesis of deoxynucleotide triphosphates (dNTPs), the building blocks of DNA, and is essential to the assembly and repair of ecDNA. BBI-825 was shown to dysregulate ecDNA-reliant cancer cell dNTP pools, deplete ecDNA, and was synthetic lethal in multiple oncogene amplified preclinical cancer models.

On November 7, 2024 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through development of potentially best-in-class IL-2 therapeutics, reported positive results from its Phase 1/2 dose escalation and cohort expansion study of AU-007 (Press release, Aulos Bioscience, NOV 7, 2024, View Source [SID1234647921]). The data will be presented in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting in Houston, Texas.

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!

Preliminary Phase 2 data reveal that a combination of AU-007 and low-dose, subcutaneous aldesleukin is clinically active in melanoma, a finding consistent with Phase 1 data demonstrating clinical activity in a range of patients whose tumors had progressed through prior checkpoint inhibitors. Data from all 77 patients show durable reductions in immunosuppressive Treg cells – a result unprecedented in the IL-2 class – with a correlation between longer progression-free survival outcomes as Treg reduction deepens.

"We believe these data represent preliminary clinical proof of concept for our unique monoclonal antibody, AU-007, and we are confident in its emerging profile as a potential best-in-class therapeutic," said Aron Knickerbocker, Aulos Bioscience’s president and chief executive officer. "We look forward to presenting a fuller and more mature set of Phase 2 data for melanoma, renal cell carcinoma and non-small cell lung cancer in the first half of next year."

Key findings from preliminary results of the Phase 1/2 dose escalation and cohort expansion study of AU-007, with data available on 77 patients as of the data cutoff date of September 28, 2024, are as follows:

A tolerable and manageable safety profile was observed at all doses evaluated in Phase 1 dose escalation.

No dose-limiting toxicity occurred throughout Phase 1 dose escalation.
Most drug-related adverse events were Grade 1 or 2 except for:
Grade 3 anemia in one patient who entered the study with Grade 2 anemia, had rapid disease progression and received only two doses of the study drug.
Grade 4 cytokine release syndrome (CRS) in one patient that resolved with steroids, IV fluids and brief vascular pressor support, and did not require tocilizumab. This patient was noted retrospectively to have subclinical elevated IL-6 (5x upper limit of normal) serum levels, likely due to an active case of gout at baseline.
Transient Grade 3 elevated lipase in one patient that was not associated with clinical symptoms and resolved without intervention.
Transient (3-7 days) Grade 3 or 4 lymphopenias in six patients. The lymphopenias were not associated with adverse outcomes. Transient lymphopenia is a known effect of IL-2 treatment as lymphocytes traffic out of blood and into tissue.
Strong evidence of anti-tumor activity was observed in heavily pre-treated patients, particularly in melanoma.

Two patients with melanoma refractory to prior anti-CTLA-4 and anti-PD-1 therapy were treated with AU-007 every two weeks (Q2W) and one administration of low-dose, subcutaneous aldesleukin (recombinant human IL-2), and experienced deep and durable tumor shrinkages of 48% and 100% in target lesions.
One patient in dose escalation with acral melanoma that progressed rapidly on prior anti-PD-1 therapy received AU-007 Q2W and one loading dose of subcutaneous aldesleukin. This patient remained on AU-007 therapy for 11 months with disease control.
Anti-tumor activity was also observed in heavily pre-treated patients with renal cell carcinoma (RCC), bladder cancer, head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) whose tumors had progressed through checkpoint inhibitors.
AU-007 and low-dose, subcutaneous aldesleukin continues to demonstrate a unique pharmacodynamic (PD) profile in the IL-2 class.

A decrease in Tregs appears to be a critical determinant of observed efficacy, with greater median decreases observed in patients receiving one loading dose of low-dose, subcutaneous aldesleukin compared to low-dose, subcutaneous aldesleukin administered Q2W. Based on the Treg reduction levels and other PD findings, the company has made the decision to use the loading dose rather than the Q2W schedule of subcutaneous aldesleukin going forward.
Greater decreases in Tregs on treatment is associated with longer progression-free survival (PFS) across the Phase 1 and Phase 2 portions of the AU-007 trial. Patients with a Treg cell reduction greater than the median of 43% had longer PFS outcomes than those with a Treg cell reduction less than the median of 43%.
The Phase 2 expansion cohorts evaluating AU-007 and low-dose, subcutaneous aldesleukin continue to enroll patients, with a focus on melanoma and non-small cell lung cancer. An additional Phase 2 cohort will evaluate AU-007 and low-dose, subcutaneous aldesleukin combined with avelumab (checkpoint inhibitor; anti-PD-L1) in NSCLC. The company anticipates presenting updated clinical data in the first half of 2025.

The poster, "A phase 1/2 dose escalation and cohort expansion study of AU-007, a human monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25 binding, plus low-dose aldesleukin in advanced solid tumors," (Abstract 685) is available to meeting registrants as an electronic poster on the SITC (Free SITC Whitepaper) 2024 virtual meeting platform. It will be presented in a poster session on Friday, November 8, 2024, 9:00 a.m.-7:00 p.m. CST in Exhibit Halls AB.

The poster presentation is also available on the Aulos Bioscience website in the Abstracts and Publications section.

To learn more about the AU-007 clinical trial program, please visit ClinicalTrials.gov (identifier: NCT05267626). For patients and providers in the U.S., please visit www.solidtumorstudy.com. For patients and health professionals in Australia, please visit www.solidtumourstudy.com.

About AU-007
AU-007 is a human IgG1 monoclonal antibody designed by leveraging artificial intelligence that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 redirects IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by effector T cells, from binding to trimeric receptors on regulatory T cells while still allowing IL-2 to bind and expand effector T cells and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to CD25-containing receptors on eosinophils, as well as vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.