Cinda failed to introduce ISAC drug clinical research and development, Bolt stock price plummeted 56%

The development of antibody-immunostimulatory conjugates (ISAC), once regarded as the next generation ADC, has once again been frustrated

On December 6, Bolt announced the latest clinical data of HER2-TLR7/8 immunostimulatory antibody conjugate (ISAC) BDC-1001 at the ESMO IO conference

BDC-1001 is a combination of HER2-targeted trastuzumab bioanalog and TLR7/8 agonist, which directly kills tumor cells and activates local phagocytosis of myeloid APC through a mechanism mediated by trastuzumab And to eliminate HER2 expressing tumor cells and T cells to exert anti-tumor activity in the long-lasting immune response to tumor-associated antigens or neoantigens

However, the clinical results are not as satisfactory as expected

Affected by this, Bolt's stock price was cut in half, plummeting nearly 56%

01 The global ISAC R&D failed one after another

Bolt Biotherapeutics is a clinical-stage biotechnology company with the Boltbody ISAC platform.

As a new immunotherapy, the Boltbody ISAC platform consists of three main components: tumor-targeting antibodies, non-degradable linkers, and proprietary immunostimulants (TLR 7/8 agonists) used to activate the patient’s innate immune system

Bolt has applied for patents for its Boltbody in many countries around the world.

Its core drug candidate, BDC-1001, is an ISAC based on this platform.

In preclinical models, Boltbody ISAC has been shown to have the ability to eliminate tumors after systemic administration, and it also leads to the development of immune memory

Image source: Bolt Therapeutics official website

From the research pipeline announced by Bolt, in addition to BDC-1001, Bolt is also simultaneously advancing BDC-2034, an anti-carcinoembryonic antigen (CEA) ISAC, and other immuno-oncology treatment pipelines

Currently, Bolt Biotherapeutics, Silverback Therapeutics, Mersana Therapeutics and other companies are developing ISAC drugs

Silverback Therapeutics focuses on the development of ADC drugs with new mechanisms.

Mersana Therapeutics focuses on ADC drug development.

Bolt is not the first failure in ISAC drug development

Silverback Therapeutics announced the phase I clinical data report summary of its new immunostimulatory ADC drug SBT6050 at the ESMO meeting held in September this year.

02 Cinda introduced Bolt, Qi De cooperated with Borui, Hengrui and Baiji self-developed

Before the R&D failure, Bolt's proprietary technology platform was generally optimistic, which also attracted the attention of Chinese pharmaceutical companies
.

In August of this year, Innovent and Bolt reached a cooperation.
Innovent used its proprietary antibody drug portfolio and undisclosed tumor target research and development capabilities, combined with Bolt's advanced ISAC technology and myeloid cell expertise to develop three new types of immunity Therapeutic drugs
.
Bolt will receive a cash down payment of US$5 million from Cinda Biotech and a potential future equity investment of no more than US$10 million
.
In addition, after reaching development and sales milestones in their respective regions, both companies are eligible to receive corresponding milestone payments and royalties
.

Coincidentally, on September 5, GeneQuantum (Qide Pharmaceutical) and BrighGene (Borui Pharmaceutical) signed an agreement on the joint development of Antibody Immune Agonist Conjugate (AIAC) GQ1007
.

Qi Tak Pharmaceutical focuses on the research and development of innovative bio-conjugated drugs, and has a core technology portfolio authorized by global patents such as enzyme-catalyzed site-specific coupling technology, innovative linker technology, and intelligent continuous coupling (iLDC) platform technology
.
And Borui Medicine has extensive experience in the development of small molecule drugs, especially in TLR7/8 agonists with its own unique advantages
.

Therefore, the cooperation between Qide Medicine and Borui Medicine is also seen as the two parties' complementary advantages to jointly accelerate the development of GQ1007
.

This is not the first collaboration between Kai Tak Medicine and Borui Medicine
.
As early as 2020, Borui Pharmaceuticals participated in the B-round financing of Qi Tak Pharmaceuticals, and established a strategic partnership with Qi Tak Pharmaceuticals to carry out global development and commercialization of several new generation ADC drugs
.

In addition to research and development through cooperation, domestic companies are also actively deploying in this field through independent research and development
.
This includes the self-research platform built by Baiji and Hengrui to develop ISAC targeting TLR7/8 and TLR7
.
According to information previously disclosed by BeiGene, its ISAC targeting TLR7/8 can activate antigen-presenting cells (APC, including Mφ, DC, etc.
), thereby killing tumor cells
.

As of now, 13 ADC drugs have been approved worldwide, and more than 230 ADC projects are in the clinical stage.
The market size is expected to reach 16.
4 billion US dollars in 2026
.
ISAC, as a kind of conjugated drug that is functionally similar to ADC, is different in that it can drive innate immunity and specific immunity, and it can also activate CD4/CD8 T cells through TLR to transform cold tumors into immune-heat tumors.
, By regulating the immune microenvironment and immune stimulation of tumors, the purpose of treating tumor diseases can be achieved
.

As a special ADC drug, the research and development for ISAC can be one of the ways for companies to achieve differentiated competition on this track
.
The characteristics and advantages of "ISAC's payload is an innate immune agonist or modulator, which can transform cold tumors into immune-hot tumors and enhance immune response", and may become a new technology leading the next generation of ADCs in the future
.