San Francisco Bay Area-based Bolt Biotherapeutics confirmed that the U.S. Patent and Trademark Office (USPTO) has issued U.S. Patent No. 10,675,358 entitled “Antibody Adjuvant Conjugates.”

Bolt Biotherapeutics a private clinical-stage biotechnology company developing a new category of immunotherapies called Immune-Stimulating Antibody Conjugate (ISAC). The platform technology is designed to harness the power of the innate immune system to treat cancer.

The patent provides protection for immunoconjugates of a piperazinyl imidazoquinoline adjuvant bound to an antibody, including Bolt’s BDC-1001 ISAC.

HER2-expressing solid tumors
BDC-1001 is being developed as a monotherapy for patients with HER2-expressing solid tumors. BDC-1001 is an ISAC comprised of trastuzumab conjugated to a Bolt proprietary TLR7/8 agonist payload.

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In preclinical models, systemic administration of HER2-ISACs demonstrated localized immune activation that results in robust single-agent activity, generation of host immunological memory against cancer, and epitope spreading.

Furthermore, preclinical data, presented at SITC 2019, showed complete, durable regression of established tumors resistant to trastuzumab (Herceptin®; Genentech/Roche) and immunological memory providing protection against tumor cells that no longer express the HER2 antigen in syngeneic mouse cancer models. This offers the potential for durable and meaningful responses for HER2-expressing cancers.

The promise of Immunological memory. Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) selectively target tumors for destruction by the immune system. Tumor-associated myeloid cells engulf ISAC-bound tumors, become armed with tumor neoantigens, and migrate to the lymph nodes where they mediate the activation and expansion of tumor-reactive T-cells. In preclinical tumor models, ISAC therapy leads to the regression of established tumors and generation of immunological memory, which guards against the recurrence of tumors that express tumor neoantigens even if they no longer express the ISAC target antigen. Image courtesy: © 2020 Bolt Biotherapeutics.

Translating scientific discovers in therapeutic agents
“The development of Boltbody™ ISACs is motivated by the insatiable need to translate scientific discoveries into products that will help cancer patients become survivors,” noted  Michael N. Alonso, Ph.D., scientific co-founder and vice president of immunology and pharmacology of Bolt Biotherapeutics.

“This patent issuance is an important milestone that provides protection for our BDC-1001 clinical asset and our Boltbody™ ISAC technology platform. Our dedicated and talented teams will continue to aggressively build a robust patent portfolio to protect our pipeline, our platform, and our commitment to patients,” Alonso added.

In March Bolt Biotherapeutics confirmed that it had started a clinical trial for BDC-1001 involving patients with HER2-expressed solid tumors. This phase I, open-label, dose-escalation, and dose-expansion study will evaluate the safety, pharmacokinetics, pharmacodynamics, and proof of mechanism of BDC-1001.

“Bolt is eager to explore the potential of BDC-1001 for treating HER2-expressing cancers, which includes patients with breast and gastric cancers that are refractory to trastuzumab and ado-trastuzumab emtansine (Kadcyla®; Genentech/Roche), as well as cancers for which no HER2-targeting therapies have yet been approved,” Schatzman said at the time of the announcement.

“We’re looking forward to working with the medical community to bring the promise of this exciting new approach to patients and anticipate initial data will drive our future development plans.”

Technology platform
The Boltbody™ platform consists of Immune-Stimulating Antibody Conjugates (ISAC) that harness the ability of innate immune agonists to convert cold tumors into immunologically hot tumors thereby illuminating tumors to the immune system and allowing them to be invaded by tumor-killing cells.

Boltbody™ ISACs have demonstrated the ability to eliminate tumors following systemic administration in preclinical models and have also led to the development of immunological memory, which is predicted to translate into more durable clinical responses for patients.

Funding
Earlier this month Bolt Biotherapeutics completed a U.S. $ 93.5 million Series C round of financing. the funding round was led by Sofinnova Investments and included additional investors RA Capital Management, Rock Springs Capital, and Samsara BioCapital.

In conjunction with the financing, Jason Pitts Ph.D., principal at Sofinnova Investments, will join Bolt Biotherapeutics’ board of directors.

“We believe Bolt is well-positioned to execute on its vision of developing immuno-oncology therapies with the potential to generate systemic immunological memory and provide durable clinical benefit. I look forward to helping the company realize its goal of developing the ISAC platform across a range of solid tumor targets,” Pitts said.

Since its founding in 2015, the company has raised more than U.S. $ 170 million. This latest funding round will be used to support the clinical development of its lead Immune-Stimulating Antibody Conjugate (ISAC), BDC-1001.

Clinical trial
A First-in-human Study Using BDC-1001 in Advanced and HER2-Expressing Solid Tumors – NCT04278144

Reference
Gingrich J. How the Next Generation Antibody Drug Conjugates Expands Beyond Cytotoxic Payloads for Cancer Therapy. ADC Review; April 7, 2020 [Article]