Closely-held KAHR Medical of Israel is seeking to raise* as much as $10-million in the U.S. and Europe to continue development of its dual signaling proteins (DSPs), including KAHR-102, its lead drug candidate for the treatment of an orphan indication in lymphoma.
“The current round will fund the company’s activities until mid-2017 and will take us to the end of our Phase 1/2a for KAHR-102 and the beginning of Phase 1/2a with KAHR-101,” CEO, Dr. Noam Shani, says in an interview with BioTuesdays.com.
Dr. Shani says the company has three funding modules in its current round. They include raising $4-million for the Phase 1/2a trial and final formulation development of KAHR-102; $3-million for basic preparations to take KAHR-102 into a pivotal trial in the orphan indication; and $3-million for KAHR-101 to upscale manufacturing and toxicology.
KAHR-102 is a liquid injectable now and Dr. Shani says the company would like to develop a lyophilized, or freeze-dried, final formulation. Lyophilization stabilizes compounds so they can be reconstituted just prior to use.
To date, KAHR has raised $14-million from its main shareholders, which include Hadasit Bio-holdings (TASE:HDST), Sanofi-Genzyme BioVentures and Thomas Eldered, the owner and CEO of Recipharm (NASDAQ OMX:RECI B), a leading European drug developer.
“If we get clear efficacy data in the Phase 1/2a trial, our consultants believe that we could apply to regulatory authorities to go directly into a pivotal trial for market approval,” Dr. Shani points out.
KAHR expects to begin the Phase 1/2a trial in patients with refractory diffuse large B-cell lymphoma (R-DLBCL) in early 2016, with data about 12 months later. “That could be a good point for a possible IPO,” he suggests.
Dr. Shani figures that if KAHR-102 reaches market, it could be used to treat other lymphoma indications as well as autoimmune indications. “Although the mode-of-action is completely different, this is a similar development pathway that IDEC Pharmaceuticals used to develop Rituximab, starting out in lymphoma and then crossing over to autoimmune diseases,” he adds.
In a best-case scenario, Dr. Shani says KAHR-102 could be on the market within five years, with sales of more than $1-billion within 10 years.
Dr. Shani has begun telling the KAHR-102 story to venture capital funds and investment bankers and he hopes to meet potential investors at the 2015 BIO International Convention in Philadelphia this month.
KAHR’s DSP technology is divided into two proprietary platforms: DSP-Hexamers and DSP-Clusters, each covering hundreds of different drug candidates. The company is developing KAHR-102 from its DSP-Hexamers and KAHR-101 from its DSP-Clusters platforms.
Dr. Shani explains that DSP molecules are fusion proteins connecting an extracellular portion of a Type-1 membrane protein at the fusion protein’s N-terminus with an extracellular portion of a Type-2 membrane protein at the fusion protein’s C-terminus.
He says this enhanced architecture of DSP molecules creates fusion-proteins with two functional ends that allow the fused molecule to facilitate a unique mode-of-action with increased activity, specificity and therapeutic benefits that cannot be achieved by simply administering the DSP protein elements as separate units, he contends.
“With two functional ends, DSP drugs are capable of effecting two biological pathways at the same time and at the same site, so that both pathways are reinforcing each other,” he points out. “The bi-functional nature of DSP molecules also allow for dual targeting of both sides of the molecule to the same site to reduce toxicity as well as the ability to utilize two biomarkers for more personalized medicine.”
According to Dr. Shani, the company’s DSP technology offers a solution to a 30-year-old problem of using tumor necrosis factors, or the TNF-superfamily of ligand proteins, which control the immune system, for treating disease.
Using the TNF-superfamily of ligands as therapeutics has been unsuccessful in the past because of toxicity and efficacy issues, he points out. “KAHR’s DSP technology offers a bi-functional solution to this problem by combining optimal TNF-family ligands structures with a second functional or targeting activity.”
In discussing KAHR-102’s mechanism of action, Dr. Shani explains that KAHR-102 is a fusion protein linking the extracellular portions of the CTLA-4 protein and FasL, a TNF-family ligand of the Fas receptor. FasL is a strong cell death receptor that is functional on cancer cells and activated T-cells. Activation of the Fas receptor leads to cell apoptosis. CTLA-4 targets and binds the B7 protein at very high affinity, turning off anti-apoptotic signals.
“Lymphoma cells and activated immune cells express both B7 and the functional Fas receptor, making them a likely therapeutic target for KAHR-102,” he adds. “KAHR-102 targets both B7 and Fas receptor, synergizing their activities to efficiently treat lymphoma and autoimmune diseases. Moreover, our data show KAHR-102 is effective on multiple human cancer cell lines, but is 100 times more effective on lymphomas.”
Dr. Shani says key opinion leaders believe that future lymphoma treatment will be based on combining targeted cytotoxic drugs with immune therapy.
“We believe KAHR-102 has the potential to find a niche in the lymphoma treatment because it is lymphoma-specific, personalized, and has a relative short half-life, which is appropriate for tumor debulking before immune-therapy.”