1. Our Company and Product
Five Element Medicines is a biopharmaceutical company committed to discovering and developing novel, first-in-class medicines to treat metabolic diseases including NASH, diabetes and dyslipidemia, and aging-related diseases such as cardiovascular diseases, cancers, and Alzheimer’s diseases to prolong the healthspan and lifespan of human beings.
Like the deep learning from Big Data, we leverage the real world data (RWD) and real world evidence (RWE) and build statistical models (1) to identify the unmet medical needs; (2) to find the active pharmaceutical ingredient (API) from natural products, or the biomarkers for the target population; (3) to support study designs in clinical development and regulatory submission; and (4) to provide values to the patients and to shape market strategy. We have the proprietary technology platforms in formulations and molecular engineering to develop the API into a viable drug candidate. This will not only significantly reduce the R&D time and cost, but also greatly improve the rate of success for drug development. In 2020, the median cost of getting a new drug into the market was $985 million with the average at $1.3 billion, and it took about 10 - 15 years. If adopting our approach, the estimated R & D cost will be only at 200 - 250 million, and the R & D time for drug approval will be shortened to only about 5 - 7 years.
Our first drug candidate is FEM-101, a small molecule derived and reformulated from a natural product. The herb has been used as medicine to treat infection, fever and GI diseases for over 3000 years, and in recent 20 years the extract from the herb in a pure chemical molecule was tested in clinical trials and has shown great activities in treating diabetes, dyslipidemia, obesity, cardiovascular diseases, and even cancer. Despite of this, the extract has a very low bioavailability at 0.5% due to very low solubility and permeability, which limited its pharmaceutical applications, and too high dose will result in toxicities.
In order to fully utilize the drug’s great potential on NAFLD and NASH, novel drug delivery methods using novel formulation technology will be explored and developed to significantly improve the drug's bioavailability by 10-20 fold, thus to improve its efficacy and at the same time to reduce the toxicities. We are currently working with the labs on the formulation, and then on CMC, and preclinical studies including pharmacologic studies, in-vitro and in-vivo, and toxicologic studies to prepare for the IND.
Our second drug candidate, FEM-102, will be derived from endotoxin to treat cancers and sepsis. From literature it was widely reported that textile and diary workers had less chance to get lung cancer, epidemiological studies have shown that endotoxin from their working environment had played an important role. After that German scientists had performed 2 clinical trials using intravenous injection of salmonella endotoxin in patients with NSCLC or colorectal cancer. Great anti-tumor activity was observed although the tolerable intravenous dose cannot exceed 4 ng/kg. The most commonly reported toxicities included fever, chills, shivering that were manageable. Our company is going to develop the drug in oral or nasal spray form so that patients can get the benefit of endotoxin to treat cancer and at the same time avoid the serious side effect. This immunotherapy will target on NSCLC and CRC. Another important indication could be sepsis, where there is no approved drug available and the market size in sepsis alone will reach $5.9 billion by 2026.
2. Market Analysis
Non-alcoholic steatohepatitis (NASH) is the advanced form of non‑alcoholic fatty liver disease (NAFLD), it is highly unmet medical needs. The progression of the disease from fatty liver, to nonalcoholic steatohepatitis, fibrosis, compensated cirrhosis, and decompensated cirrhosis will eventually lead to hepatocellular carcinoma, liver transplantation, cardiovascular comorbidities, and death. Its economic and clinical burden is enormous. It was estimated that about 30-40% American adult had NAFLD and 17.6 million had NASH in 2016, and NASH population will climb to 27.0 million in 2030. The lifetime costs of all NASH patients in the United States in 2017 was estimated at $222.6 billion.
So far, over 90 compounds were tested in clinical trials, only very limited have shown promise. Of note, Intercept’s OCA showed mild improvement in fibrosis but not in NAS score in Phase 3 study. FDA rejected the accelerated approval because the mild improvement in fibrosis cannot outweigh the induced risks with over half got pruritus. The other two leading candidates are Madrigal Pharmaceutics’ Resmetirom (a thyroid hormone receptor) and Akero’s efruxifermin (a FGF21 receptor), showed better efficacy and safety compared with other drugs in Phase 2 clinical trials. The reason for the failure of so many compounds is due to the simple mechanism of actions (MOA) of monotherapy, calling for the combinations of multiple compounds.
Compared to these compounds, we believe that our drug candidate FEM-101 will have great competitive advantages in terms of efficacy and safety. First, the herbal extract has shown not only significant reduction in blood glucose, HBA1c, insulin, and insulin resistance, but also significant reduction in cholesterol, LDL, triglycerides, and body weight (and increase in insulin sensitivity and HDL) in over 50 randomized clinical trials. Second, in a randomized study on patients with NAFLD, the herbal extract plus lifestyle change resulted in a significant reduction of hepatic fat content (HFC) (52.7% vs 36.4%, p = 0.008) when compared with lifestyle change alone after about 4 months of treatment, paralleled with better improvement in body weight, HOMA-IR, and serum lipid profiles. Third, it showed protective effect on the heart by improving LVEF in a randomized study. And finally, the drug has a very good safety profile. It is safe and well tolerated, only mild and moderate GI toxicities (nausea, constipation, and gastric discomfort) have been reported.
3. Our Management Team
Our leadership team consists of individuals in drug development with track records of success for about 10 drug’s approval, from CMC, pre-clinical to clinical in oncology, diabetes, infectious, and cardiovascular diseases. Our expertise in drug development strategy, smart study design will greatly improve the efficiency and chance of success for drug development.
Junming Zhu, Ph.D, CEO, has over 25 years in drug development. He has worked in leadership roles in biostatistics and data management at multiple pharmaceutical companies including Eli Lilly, Eisai, and Roche, and contributed to the approval of 6 drugs (atezolizumab, levatinib, cetuximab, necitumumab, Glucophage XR, and olaratumab) and 2 companion diagnostics (SP-142 and SP-263). He is expert in RWE and smart study design and have incorporated it into clinical development and NDA submissions for several drug pipelines.
Yue Lu, Ph.D, CSO, has 25+ years’ pharmaceutical industry experiences. Successful track record of transforming development-stage drug candidate into commercial launch. For example, he turned the API into approved drugs for IMBRUVICA™, Telotristat Etiprate™, and Sotagliflozin™. He holds over 15 patents and was the winner of 2019 ACS Heroes of Chemistry Award. He will lead the technical aspects for the formulation, CMC and preclinical studies.
Michael Ezrokhi, Ph.D, our consultant in clinical development, has over 20 years’ experience in metabolic and cardiovascular drug development. He was the lead scientist at VeroScience.
4. Fund Request
We plan to raise 2 million dollars to develop the optimal formulation by utilizing the proprietary platforms to significantly improve the drug's bioavailability, and potentially improve its efficacy and at the same time reduce the toxicities. We are currently working with the lab to prepare for the formulation, and it is expected by the end of 2021 we should have the optimal formulation determined.
The following are the objectives for the formulation and relevant animal studies:
1. Explore more salts/cocrystals with the active pharmaceutical ingredient (API) to find optimal salt(s)/cocrystal(s) with high solubility.
2. Explore formation method of amorphous form of the API using crystal engineering
3. Explore solid dispersion technique to the promising salt/cocrystal selected from 1 or amorphous form from 2 and desired polymer(s):
a. Spray-drying: the challenge is to find at least one volatile solvent to dissolve API
b. Melt extrusion: the challenge is to find a suitable API from 1 with not-very-high melting point.
4. Test the optimal salt(s)/cocrystal(s) for pharmacokinetics and bioavailability on animals. Based on mean plasma concentration-time profiles of the formulation following intragastric administration and pharmacokinetic parameters, select the most promising salt/cocrystal for formulation development incorporating permeation enhancers.
5. Based on the optimal formulation, patent will be filed to protect the intellectual property.
6. The optimal formulation will be tested on animal for single dose and multiple dose toxicity to determine the MTD dose for animals, which will be used to project the dose for FIH clinical study.
7. The optimal formulation will also be tested in in-vitro and in-vivo studies to show the efficacy in the animal models with NAFLD and fibrosis and to determine the biological effective dose.
We will have to raise $10 – 40 million in Round A to prepare for CMC, preclinical studies for IND and Phase 1 and 2 clinical studies.