BioSpace learned that growing functional organs may indeed be possible, and about the role of protein-to-protein interactions in cancer immunotherapy.
The hybrid BIO CEO & Investor Conference 2022 held February 14th through 16th was an opportunity to hear from established and emerging public companies as well as a select number of private biotech companies. Here are two companies that caught the attention of BioSpace – one with breakthroughs in organ engineering, and the other with a novel approach to cancer immunotherapy.
ACRO Biomedical Co., Ltd. is developing biomaterials from animals to regenerate human tissues and organs, with the goal of making tissue and organ transplantation readily available and affordable.
That program is built atop a product line of natural biomaterial scaffolds. The scaffolds are created using ACRO’s proprietary supercritical CO₂ extraction technology to remove cells, fat and non-collagenous proteins from animal tissues and organs, while leaving collagen scaffolds intact. Those scaffolds are used in medical devices in a variety of fields, including ophthalmology, wound care and neural surgery. Notably, the process does not disrupt the natural collagen scaffold structure and does not require chemical solvents.
By combining this technology with stem and/or somatic cells for human cell therapy, growing functional organs appears possible.
“Our goal is whole-organ engineering for the heart, liver and kidney transplantation,” ACRO CEO Dar-Jen Hsieh said. “We wish to recellularize the organ scaffold in vivo for autologous organ transplantation by grafting the decellularized natural organ scaffolds back into the live animal or human body.
“For proof of concept, we did a rabbit heart reconstruction,” Hsieh continued. “A surgeon put the decellularized rabbit heart into a rabbit to grow in its abdominal cavity, closed the cavity and waited.” A slide showed the blood flow forming in the tissue. “If it works, the rabbit will have two hearts pumping at the same time.” At that point, the heart would be ready for transplantation. A rabbit kidney reconstruction also is underway.
ACRO also demonstrated success implanting an artificial cornea graft, making it the first such successful graft in the world, Hsieh said. In it, a pet dog named Bunny had a damaged, turbid cornea. A month after the surgery, Bunny’s cornea was clear, with no signs of rejection. A human cornea graft trial has begun in four medical centers in Taiwan, with completion expected later this year.
Additionally, research involving the ACROGEN ADM particle (a dermal filler) “shows that when you put the particles under the skin, you see new collagen formation and new hair follicle regeneration.” A slide showed that even nude mice grew hair. “This hair follicle regeneration made us so excited, we wrote a new patent,” Hsieh said.
The company enables many options for tissue regeneration. Its approved products include collagen scaffolds (for nerves, brain, blood vessels, whole skin, dermis, cornea, bone, liver, etc.) on which scientists can culture stem cells or somatic cells for tissue engineering, or they can grind the scaffolds into powders for 3D bio-printing. Various shapes of implants also are available, including a Lego®-like bone graft that can be assembled.
ACRO holds 43 international patents across the U.S., Taiwan, China, Japan, Korea, India, Hong Kong and EU. Some 20 more are pending. Its orthopedic products hold approvals from the U.S., Singapore, Taiwan, Philippines and Vietnam. In terms of stock, this year it plans to apply for listing on the Over the Counter (OTC) market.
Balto Pharmaceuticals, Inc., also presenting at the conference, is developing a cancer immunotherapy based upon targeted disruption or degradation of protein-to-protein interactions.
“Protein-to-protein interactions are the molecular basis of cancer cell proliferation. Therefore, targeting protein-to-protein interactions has great potential for cancer treatment,” said Balto CSO C. Wilson Xu, Ph.D.
Balto’s platform, dubbed Protein-Protein Disruption/Degradation (PP2D), is based upon the work Xu did as a postdoctoral fellow at Harvard University. In it, “We load wells with engineered cells, load the chemical library, incubate the wells and then can identify the protein-protein interaction (PPI) disruptor,” he said. “This can be used for drug development for virtually any PPI disruption.”
Balto’s small molecule programs are in early development for transcriptional complex, allele-independent K-Ras/X and other PPIs. The company is focused upon two assets: BP36 and PP2D. Most of this presentation addressed BP36.
Early studies involving multiple cancer cell lines show cancer inhibition in vitro and in mouse models. As evidence, Wu showed slides of a BP36-treated tumor and a vehicle-treated tumor. Approximately 98% of the BP36-treated tumor was composed of lymphocytes – “mostly T and B cells” – and about 2% cancer cells. In contrast, the vehicle-treated tumor was nearly 100% cancer cells with no lymphocytes. Another slide showed a number of tertiary lymphoid structures – which are associated with favorable clinical outcomes – in BP36-treated tumors, but non in the vehicle-treated tumors. Both slides “indicate that BP35 turns immunologically cold tumors hot by recruiting a massive number of lymphocytes,” Wu explained.
Balto is working now to understand the molecular mechanism by which BP36 tumors recruit lymphocytes by analyzing the molecular markers of cancer cells and their associated lymphocytes.
Wu suggested that Balto’s approach could be used to treat cancer patients that do not respond to immune checkpoint therapy because its mechanism of action is different. “About 80% of cancer patients do not respond to immune checkpoint therapy, and some patients develop resistance to therapy after an initial response,” he pointed out. “BP36 targets a protein complex that is dysregulated in more than 30 different types of solid tumors.”
Balto plans to raise $5 to $15 million in Series A funding to expand development of PP2D and perform IND-enabling studies of BP36 or its analogs.
