CEO Conversations XXVII: Ben Chien, Ph.D., Founder, Chairman & CEO of Foresee Pharmaceuticals (6576 TT)
Photo Credit: money.udn.com
Foresee Pharmaceuticals has accomplished more in its nine years history than virtually any other Taiwan biotech company in that time frame. During this short history, the Company has successfully licensed out its lead clinical product, CAMCEVI™, for US$ 420mn. This is the second largest drug licensing contract after Oneness’ US$ 520mn deal. Moreover, the drug has already received US FDA approval and is scheduled for commercial US launch in early 2022.
Foresee was created as a spin-off of the R&D department of QPS, a renowned CRO in the US. The founder of QPS, Dr. Ben Chien, is himself a serial entrepreneur, and is also the Chairman & CEO of Foresee Pharmaceutical. Through this new establishment, Dr. Chien combined previous experiences and resources, utilizing cutting-edge innovation, to solve the problems physicians and patients face in current medical treatment.
The key strength of Foresee Pharma is the agile and fast-to-market application of its innovative drug delivery platform which greatly simplifies the administration of currently available products. At the same time, Foresee also has two first-in-class innovative drugs with a broad range of targeted indications.
Products that tested in or have been passed Clinical Trial
Fast-to-Market, Low Cost, High Return “SIF” Platform
Foresee primary drug delivery innovation is a stabilized injectable formulation (SIF) platform technology. The drug delivery system consists of biodegradable materials dissolved in biocompatible solvents and combined with a bioactive agent that is modified to achieve an optimal formulation stability and release profile. The enhanced stability allows the formulation to be pre-filled into a ready-to-use syringes with an extended storage shelf-life. The fill-finished product can be conveniently administered to patients via a small gauge needle to form a depot in situ. The bioactive agent encapsulated in the depot is then released in a controlled manner through diffusion and biodegradation of the depot matrix. The SIF drug delivery system can be designed to achieve a customized controlled-release profile over a period ranging from days to months.
To date, the SIF delivery system has demonstrated its applicability to a wide range of small molecules and peptides. SIF technology is most effective for protein drugs that are not suitable for oral dosage and thus need daily injections or high potency drugs taken in small dosages each day. The lead product of the SIF platform, CAMCEVI™, was approved by the US FDA and will launch in 2022.
The active ingredient of CAMCEVI™ is leuprolide and is indcated for the treatment of prostate cancer. Currently there are two major leuprolide products: Abbvie/Takeda’s Lupron Depot®, and ELIGARD® of Tolmar Pharmaceuticals. Both products are very difficult to use as there is a complex process for medical professionals to premix the drug before usage and the drug is good for only 30 minutes to 2 hours after mixing. The complex mixing steps not only increase the risk of contamination, but cannot guarantee the patients can receive the correct dosage. This brings higher risk for patients who need drugs to control hormone levels.
Leveraging SIF technology, CAMCEVI™ can be manufactured and supplied in a ready-to-use syringe with a long shelf-life of six months. No premixing is required; hence no problem of needle clogging and inaccurate doses.
“The reason we choose leuprolide as our first product is the huge market for prostate cancer, and leuprolide is the largest category in this therapeutic area. We believe that we can overcome the technology hurdle, differentiate ourselves from our peers and raise the barrier for competitors to join this market. One example is Abbvie’s Lupron Depot which has been approved for 32 years already and still there is no generic player in the market.” Said Dr. Chien.
It is expected that the global leuprolide market will grow by US$ 1.0bn during 2022-2026, to US$ 3.5bn with a CAGR of 7.4%. Of this market increase, 44% will originate from North America. Foresee Pharma has completed a global licensing agreement with a total contract value of US$ 420mn in milestone payments but not including royalties. It is the 2nd largest licensing deal in the Taiwan biotech industry, second only to the US$ 530mn licensing deal of its atopic dermatitis new drug in 2020. CAMCEVI™’s commercial launch in the United States is scheduled for 1Q2022. At the same time, the Company is expecting EU approval and a NDA application submission for its 3-month formulation.
Foresee is developing other hormone therapies with SIF technology, such as Goserelin and Triptorelin, targeting to further expand its market share in prostate cancer. “The development period for CAMCEVI™ is a bit longer than we expected. But we have learned a great deal from this experience, from formulation, CMC and the entire regulatory process. The next two products are very much like leuprolide so basically we just go through the entire process again, but will be more cost and time-effective this time. We had completed the formulation of Triptorelin for 3 and 6-month dosage, and Goserelin 3-month dosage. The clinical trials of these drugs are ready to go after the CMC is ready. The development process of these two drugs will be much faster than CAMCEVI™. From a drug development point of view, these are the low hanging fruits” said Dr. Chien. ”On the other hand, we are studying the application of the SIF platform for neurology. Currently, we are finalizing the formulation of three new products for two billion-dollar therapeutic areas, and targeting to start clinical trials in 2023.”
Innovation from Drug Discovery
Foresee owns two innovative drug platforms: ALDH2 activator and MMP-12 inhibitor. Both are in translational process and aim to translate the efficacy and safety profile found in animal models to human data. After proof of concept, Foresee will start to expand the indications for further development.
ALDH2 Activator
ALDH2 is a key mitochondrial regulator of toxic aldehyde metabolism, transforming toxic aldehyde to relatively harmless ester. If aldehyde aggregates in the human body due to a low presentation of ALDH2, it will combine with DNA to form aldehyde-DNA adducts and cause problematic protein structure and diseases. High energy consumption organs like the brain, kidney and heart have a lot of mitochondria working in the tissue. Histologic sections and biopsy evidence show ALDH2 presentation is lower in lesion tissue and activating ALDH2 can improve the health of these tissues.
“Dr. Mochly-Rosen from the Stanford University discovered this mechanism and the molecule Alda-1, also an ALDH2 activator. However, to be used as a drug, Alda-1 does not have a good dosing property. Our Chief Scientific Officer Dr. Wenjin Yang helped to synthesize a next-generation ALDH2 activator with better activity and suitability to use as a drug. Dr. Yang told me about his project; I found it very interesting; so we licensed the project in.”
The first indication chosen for the new ALDH2 activator, FP045, is Fanconi anemia (FA). Fanconi anemia is a rare pediatric disease. One study published in Orphanet defines the prevalence of the disease as 1-9/1,000,000 putting the estimated prevalence in the US at 2,954 patients. This genetic disorder is often characterized by physical abnormalities, bone marrow failure, and/or an increased risk of malignancy. Bone marrow failure occurs in 75 – 90% of patients and is often diagnosed before the age of ten. The life span of the patients is between the age of 20 to 30.
Studies of the factors contributing to bone marrow failure in FA patients have suggested that acetaldehyde and formaldehyde are important contributors to interstrand cross-link (ICL) formation, a DNA defect that is typically repaired by the FA pathway. ALDH2, which is responsible for detoxifying acetaldehyde as well as other aldehydes, may be important in the maintenance and survival of hematopoietic stem cells. So far, this enzyme has been shown to modify the development of the disease in mice.
Developed by Foresee Pharma, FP-045 is a potent and highly selective ALDH2 activator, highly soluble and orally available. In vitro study demonstrated the capability of FP-045 to increase ALDH2 activity and protect cells from damage due to exposure to toxic reactive aldehydes. The data supports the potential of the drug to maintain the development of blood cells in Fanconi anemia patients, and for patients with incipient bone marrow failure. The only treatment options available now are steroid medications and bone marrow transplant. If FP-045 is approved, it will be the only drug indicated for Fanconi anemia.
Dr. Chien said: “The patient recruitment for Fanconi anemia trial is quite challenging. Firstly, there are only 3,000 patients in the US. Secondly, it is hard for patients to travel to designated hospitals for the trial during the COVID pandemic. We discussed with FDA and they agreed that we can reduce the subject number for the trial. In collaboration with our experienced partner, we hope to initiate the Phase II trial in a few months and get the results within three years. We also are planning to expand the indication to other metabolic diseases for the next step, and will enter into Phase II trial in 2023.”
MMP-12 Inhibitor
Matrix metalloproteinase-12 (MMP-12) as a treatment target is not a new idea. However, no product that is both safe and efficacious has been developed to date. The key challenge to development is selectivity. If the compound is not selective enough, the drug will bind to other MMPs. There are more than 20 MMPs in the human body, and some of them are antagonistic to each other. Targeting the wrong MMP will lead to poor efficacy or side effects. ”We designed this new compound and own the patent. Foresee’s FP-025, is a potent and highly selective MMP-12 inhibitor. In the proof-of-mechanism trial, we didn’t see any considerable side effects or lack of efficacy as were faced by our peers like Pfizer and AstraZeneca. If we can prove the efficacy in human trials, FP-025 will be the first MMP-12 inhibitor eligible for commercialization,” said Dr. Chien.
“We have already seen the efficacy in house dust mite-induced animal models and found anti-inflammatory and anti-fibrosis properties in the kidney, brain and lung. Currently, FP-025 is in two clinical trials: one for allergic asthma and the other for ARDS induced by COVID infection. Both trials are very important to the project. People know that COVID complications are related to important organs like the brain, lung and kidney. If we can demonstrate positive results in the trial, not only can we help COVID patients, but we can also prepare for the next wave of virus infection. More importantly, we can collect data in different organs for the development of other indications. We are ready for the discussion of out-licensing after the first-in-human results are ready in 4Q2022,“ said Dr. Chien.
Other than FP-025 for acute exacerbation of asthma, COPD and ARDS, Foresee is also developing FP-020 for chronic disease applications. Indication candidates include sarcoidosis, idiopathic pulmonary fibrosis (IPF), scleroderma and emphysema. Only limited treatment options exist for these diseases which thus offer immense commercial potential.
Targeting to make Foresee a multi-billion company in 5 years, forge the company into a holding company in the long run
Dr. Chien also shared his long-term view of Foresee: “I believe all the aforesaid projects can achieve major milestones, out-licensing agreements, or marketing approvals in the next five years. And we will keep exploring new opportunities including new indications and new molecules. Not only we will have more products from the SIF platform, but also the second or third generation products will be developed for our innovative new drug.” Said Dr. Chien with confidence: “Our projects on hand are merely the first step. In the future, we will delve into a more flexible business model. For example, we can spin-off new companies with consolidated indications and projects so that investors can pick the topic of their interests. With more agility in the capital market, we could gain more resources and talent. These companies can also look for the most suitable capital market for potential IPO. Foresee could be a multi-national holding company.”
Taiwan Biotech Sector is staking up its Power
Finally, as we talked about the Taiwan biotech sector in general, Dr. Chien is pretty optimistic: “When I came back to Taiwan and started Foresee Pharmaceutical, I had hoped to can contribute my knowledge and experiences to this sector. Recently we can see more and more achievements happening in this sector. In the past, people don’t really understand biotechnology and don’t believe this is a solid industry. Now, the industry has trained more people with enough hands-on experience and knowledge to create the critical mass for a sustainable and growing industry. I believe we can be a very successful cluster around the globe, just like Japan where some companies transformed into multi-national companies.”
If you would like to arrange a meeting with Foresee’s Founder - Dr. Ben Chien, please contact yvonnehuang@qtumic.com.
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