A Brief History of the Development of SG1002
The First Oral Hydrogen Sulfide Prodrug
Gabriel Gojon-Romanillos had a brilliant insight that allowed him to foresee the use of metal sulfides and hydrogen sulfide (H2S) as extremely potent reducing agents capable of exerting therapeutic effects on mammals affected by pathologies originating in oxidative stress.
Pioneering studies initially involved the development of gastroprotected formulations of inorganic sulfide compounds such as sodium sulfide and their oral administration, to many terminal cancer patients, as well as to individuals affected by serious cardiovascular pathologies, always under medical supervision.
Dr. Gabriel Gojon-Zorrilla joins his son in the effort as head of R&D in order to help in developing a prototype of an improved H2S donor capable of slow and sustained release of H2S (i.e., an H2S prodrug).
Dr. Gabriel Gojon-Zorrilla with his son Gabriel Gojon-Romanillos
Dr. David J. Lefer, a well-known expert in H2S signaling then at Emory University School of Medicine, Atlanta, GA., starts a research collaboration with Dr. Gojon-Zorrilla and Gabriel Gojon-Romanillos.
Dr. David J. Lefer, Ph.D
Dr. Gojon-Zorrilla discovered that highly subdivided elemental alpha-sulfur containing small amounts of coprecipitated sodium sulfate and traces of sodium thiosulfate and sodium polythionates could be obtained by chemical synthesis.
When a chow formulated to contain a small percentage of this composition (code named SG1002) was fed to mice at Emory University, SG1002 yielded blood and tissue H2S concentrations equal to or higher than those obtained by intraperitoneally injecting DATS (garlic-derived diallyl trisulfide).
Dr. Felipe Arturo Morales, MD, PhD, conducted — in Monterrey, Mexico — “A randomized clinical study assessing the effects of the antioxidants, resveratrol or SG1002, a hydrogen sulfide prodrug, on idiopathic oligoasthenozoospermia” and was able to prove that subjects suffering from oligoasthenozoospermia (a condition that leads to male subfertility) could benefit from treatment with orally administered SG1002. Dr. Morales is Director of the Reproductive Medicine Center at Hospital Universitario Dr. José E. González, Nuevo León Autonomous University (UANL), Monterrey, Mexico.
Dr. Alberto Siller, MD (Certified Pediatric Oncologist) undertook a consecutive case series study in Monterrey, Mexico involving eleven children ages 18 months and over and two adults. In all cases the patient’s condition improved —in particular fatigue, inflammation, pain, headache, cardiac function and glycaemia improved, tumors shrank or disappeared. These results are described in US Patent 87717552.
In view of the aforementioned developments, Gojon-Romanillos and Gojon-Zorrilla founded a pharmaceutical company: Sulfagenix Inc. It was incorporated in Delaware. Two more scientists joined the team: Drs. Anthony T. Giordano (the first Sulfagenix Chairman and CEO) and John Elrod.
Dr. Anthony T. Giordano
Former Sulfagenix Inc.'s President and CEO
He managed the completion of a Phase I clinical study.
Gojon-Zorrilla developed, validated and documented detailed methods for determining particle size distribution, percent elemental sulfur, percent sodium sulfate, percent residual solvents, etc., which were then shared with Dr. Lefer’s team.
Gojon-Romanillos and Gojon-Zorrilla went on to examine the effects of exogenous H2S therapy — mediated by SG1002 — in a murine model of pressure overload-induced heart failure. The results demonstrated that oral SG1002 therapy prevents the transition from compensated to decompensated heart failure, in part via upregulation of endothelial nitric oxide synthase and increased nitric oxide bioavailability (Kondo K. et al., 2013, “H2S protects against pressure overload-induced heart failure via upregulation of endothelial nitric oxide synthase”, Circulation, 127:1116-1127).
Dr. Henry Krum ✝︎ (1958-2015)
Internationally-recognized heart failure researcher at
Monash University (Melbourne), served as principal
investigator for SG1002 Phase I Clinical Trial.
Dr. Henry Krum (now deceased), was an internationally-recognized heart failure researcher at Monash University (Melbourne, Australia), and served as principal investigator for the SG1002 Phase I clinical trial. Dr. Giordano was in charge of coordinating all aspects of the trial, while Gojon-Romanillos and Gojon-Zorrilla helped drafting the clinical trial investigator brochure and provided advice (both conceptual and practical) on compounding, formulation, oral dosage form, etc.
According to highly regarded experts (John L Wallace et al., 2018; Cao X et al., 2018), “SG1002 for cardiovascular disorders and ATB-346 for arthritis have progressed into clinical trials and have shown considerable promise (…) SG1002 produces more sustained and consistent levels of hydrogen sulfide in plasma (…) Sulfagenix has demonstrated that administration of SG1002 can restore to normal the plasma H2S and no levels in CHF patients, thereby reducing the severity of, or preventing, heart failure (…) Importantly, the levels of hydrogen sulfide in these subjects (i.e., the volunteers participating in the phase I clinical trial) remained below cytotoxic concentrations”. The authors conclude that “there is now some solid evidence that H2S-based therapeutics have considerable promise for a number of indications… Interestingly, a promising outcome has been observed for some pediatric cancer patients as described in patent US8771755.”
The future of SG1002 looks brighter than ever. SG1002 has been mentioned in over 180 scientific papers and meeting abstracts. The results of research involving it and carried out in different animal models by multiple investigation groups in USA, Europe, and Mexico have been highly encouraging.
Furthermore, overwhelming evidence (Gabriel Gojon and Guillermo A. Morales, 2020; “SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs”; “Anti‐inflammatory and antiviral roles of hydrogen sulfide: Rationale for considering H2S donors in COVID‐19 therapy”) now supports the view that H2S donors will soon prove their therapeutic value in a large number of indications, including infections by enveloped viruses, diabetes, fibrotic diseases, pathologies derived from ischemia-reperfusion damage, hyperproliferative diseases (including cancer), neurodegenerative diseases, gastrointestinal pathologies, pre-eclampsia, arthritis, cardiovascular diseases, hepatic and renal diseases, autoimmune pathologies, systemic sclerosis, multiple sclerosis, Duchenne muscle dystrophy, allergies, osteoporosis, sarcopenia, hearing loss, lens opacification, testicular dysfunction, male sub-fertility, erectile dysfunction, periodontitis and aging.
In the cardiometabolic and oncologic settings, current evidence supports the view that H2S-based treatments are often capable not only of achieving long-term functional recovery, but also leading to the reversal of damaged tissues and organs.
Therefore, we confidently predict that “the impact of SG1002 on global health and healthy longevity will be comparable to that of antibiotics”.
In relation to the COVID19 actual situation a provisional patent application titled: “Pan-antiviral compositions of matter and method for their development and use” (application number: 63/019,757) was submitted to the USPTO.
The collaboration's outcome included two publications: a review article (Predmore B.L. et al., 2012, “Hydrogen sulfide in biochemistry and medicine”, Antioxidants and Redox Signaling) and the Circulation’s article mentioned previously. It is worth mentioning that the reviewed article has accrued over 300 citations to this date.
Dr. Gojon and son traveled to Los Angeles in order to present a poster (Kondo K., Bhushan S., Condit M.E., King A.L., Predmore B.L., Wang R., Gojon G. (Sr), Gojon G. (Jr), Lefer D.J.; “H2S protects against pressure overload-induced hypertrophy and heart failure”) at the Scientific Sessions of the American Heart Association.
Dr. Gojon-Zorrilla at the invitation of the organizers of the Second International Conference on Hydrogen Sulfide in Biology and Medicine (H2S 2012) (Atlanta, USA, Sep 2012) gave a presentation titled “Hydrogen Sulfide Prodrugs”.
Australian CRO IDT(Australia) carried out the preparation of the first multi-kilo lot of SG1002 under cGMP conditions. After only two exploratory small-scale runs aimed at familiarization of IDT personnel with the process developed, IDT was able to scale it up and obtain, on December 2013, a 6 kg lot of SG1002 that was within specifications previously set by Dr. Gojon and Dr. Giordano.
Dr. Gojon-Zorrilla at the invitation of the Secretariat of the Third International Conference on Hydrogen Sulfide in Biology and Medicine (Kyoto, Japan, June 2014) gave a presentation titled “Phase I Heart Failure Clinical Trial to Evaluate the Safety of SG1002- a Novel H2S Donor”.
In the double-blinded, placebo-controlled, dose-escalation study — which involved both healthy and heart failure subjects — doses of up to 800 mg twice daily for seven days were well tolerated with minimal side effects. Dr. Gojon and son’s findings prove that SG1002 increases blood hydrogen sulfide and nitric oxide levels, and suggests that it attenuates increases in Brain Natriuretic Peptide (BNP) in heart failure patients (Polhemus D.J. et al., 2015)