Aulos Bioscience Provides Positive Interim Phase 1/2 Data From AU-007 at 2024 ASCO Annual Meeting
May 23 2024 - 4:05PM
Business Wire
Preliminary results show durable anti-tumor
activity in multiple solid tumor types among heavily pre-treated
patients, including patients whose tumors have progressed through
checkpoint inhibitors
The results confirm the ability of AU-007, a
human IgG1 monoclonal antibody designed using artificial
intelligence, to harness the power of interleukin-2 (IL-2) to
reduce solid tumors, and support ongoing and planned Phase 2
expansion cohorts in combination with low-dose aldesleukin in
melanoma, renal cell carcinoma and non-small cell lung cancer
Aulos Bioscience, an immuno-oncology company working to
revolutionize cancer care through the development of best-in-class
IL-2 therapeutics, today shared interim results from its Phase 1/2
trial of AU-007, the first human monoclonal antibody designed using
artificial intelligence to be tested in a clinical trial. The data
will be presented in a poster session at the American Society of
Clinical Oncology (ASCO) 2024 Annual Meeting in Chicago,
Illinois.
“The level and scope of anti-tumor activity we’re seeing across
solid tumor types are remarkable so early in clinical development,
particularly the partial responses and metabolic complete response.
The durability of the tumor reductions seen in several patients
suggests the formation of immune memory of the cancerous cells.
These results validate our long-held belief that AU-007 could widen
the therapeutic window of IL-2 by redirecting IL-2 toward CD8+ T
and natural killer cells that can kill tumor cells and away from
immunosuppressive regulatory T cells and the vasculature,” said
Aron Knickerbocker, Aulos Bioscience’s chief executive officer.
“While other developmental IL-2 therapies focus on changing IL-2
itself, AU-007 is a human antibody that is a well-established
therapeutic modality. This provides sources of advantage and
differentiation. As we treat patients in earlier lines of therapy,
we are confident AU-007 is emerging as a potential best-in-class
regimen.”
Key findings from the updated results of the AU-007 Phase 1/ 2
study, with data available on 59 patients as of the data cutoff
date of April 9, 2024, are as follows.
Well-tolerated safety profile:
- No evidence of vascular leak syndrome or pulmonary edema
reported at all dose levels evaluated.
- All drug-related adverse events were Grade 1 or 2 except for:
- One patient with Grade 4 CRS that resolved quickly with
steroids. This patient was noted retrospectively to have
subclinical elevated IL-6 serum levels at baseline.
- Five patients experienced transient (3-7 days) Grade 3 or 4
lymphopenias that 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.
- One patient with Grade 3 anemia who entered the study with
Grade 2 anemia.
Profound and durable tumor shrinkage observed in multiple
tumor types:
- A patient with large-volume metastatic melanoma whose tumors
had progressed through anti-PD-1 and anti-CTLA-4 checkpoint
inhibitors was treated with AU-007 (9 mg/kg) and one 135K IU/kg low
dose of IL-2 and experienced 76% shrinkage (unconfirmed partial
response) in target lesions at 8 weeks.
- Another patient with metastatic melanoma whose tumors had also
progressed through anti-PD-1 and anti-CTLA-4 checkpoint inhibitors
was treated with AU-007 (4.5 mg/kg) and one 15K IU/kg low dose of
IL-2 and achieved 48% shrinkage in target lesions.
- A patient with head and neck cancer whose tumors had progressed
through an anti-PD-1 checkpoint inhibitor was treated with AU-007
(4.5 mg/kg) and 45K IU/kg IL-2 dose every two weeks and experienced
32% shrinkage (confirmed partial response) in a cervical bone
metastasis, as well as reduced pain and improved motor function in
an affected hand.
- A patient with bladder cancer whose tumors had progressed
through an anti-PD-L1 checkpoint inhibitor was treated with AU-007
(4.5 mg/kg) and one 45K IU/kg IL-2 dose and achieved a durable
metabolic complete response.
- Additional tumor shrinkages were observed in patients with
widespread large-volume disease in renal cell carcinoma (RCC),
non-small cell lung cancer (NSCLC) and MSI-stable (MSS) colorectal
cancer.
Unique pharmacodynamic (PD) and pharmacokinetic (PK) profiles
in the IL-2 class:
- Decreases in peripheral regulatory T cells (Tregs) and
increases in CD8/Treg ratios demonstrate AU-007’s ability to
redirect IL-2 and prevent the negative feedback loop to Tregs.
AU-007 and low-dose aldesleukin also substantially increases
peripheral natural killer (NK) cells.
- AU-007 PK demonstrates dose-proportionality over the dose range
tested and no signs of neutralizing anti-drug antibodies (ADAs)
activity, and a half life of 15+ days.
The Phase 2 expansion cohorts of the AU-007 study are continuing
to enroll patients with a focus on melanoma and RCC. The company
anticipates presenting updated clinical data in the second half of
2024. Additional Phase 2 expansion cohorts are planned to evaluate
AU-007 and aldesleukin in second-line PD-L1+ NSCLC, with and
without the PD-L1 antibody avelumab.
The poster, “Updated results of a phase 1/2 study of AU-007, a
monoclonal antibody (mAb) that binds to IL-2 and inhibits CD25
binding, in patients with advanced solid tumors,” (Abstract 2527)
is available to meeting registrants as an electronic poster on the
ASCO online meeting platform and will be presented live in the
poster session “Developmental Therapeutics—Immunotherapy” on
Saturday, June 1, 2024, 9:00 a.m. to 12:00 p.m. CDT.
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 using
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 leverages 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.
About Aulos
Aulos Bioscience is an immuno-oncology company working to
revolutionize cancer patient care through best-in-class IL-2
therapeutics that direct patients’ immune systems toward killing
tumor cells. Matching world-class machine learning from co-founder
Biolojic Design with an in-depth understanding of the immune
system, Aulos’ initial clinical candidate, AU-007, is a
computationally designed human antibody that harnesses the power of
IL-2 to induce tumor killing while limiting the immunosuppression
and toxicities typically associated with this validated pathway.
The company was founded by Biolojic Design and Apple Tree Partners
(ATP) and is led by pioneers in the field of artificial
intelligence, antibody development and cancer immunotherapies. For
more information, visit www.aulosbio.com, X (@AulosBioscience) and
LinkedIn.
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Contact: info@aulosbio.com Media inquiries: Mike
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