Dr. Sami Said
"The Son of a Coptic Priest & Discoverer of VIP"
At 85 years of age, Sami I. Said, MD, Distinguished Professor at Stony Brook University School of Medicine in New York and former Chief of the Pulmonary and Critical Care Division and Associate Chief of Staff for Research at the Veterans Administration Medical Center in Northport, New York, was just as passionate about his research in pulmonary circulation and pulmonary vascular pathobiology as he had ever been. Up until his death on April 30, 2013, Sami was still an active member of the American Thoracic Society (ATS), served as Chairman of the National Organization for Rare Disorders (NORD) Medical Advisory Committee, and was an active participant in the biannual Grover Conference.
Sami was born in Cairo, Egypt, where he trained as a medical doctor and worked at the Naval American Research Unit. In 1953, he came to the United States on a Fulbright Scholarship. Sami completed his internal medicine residency and cardiology fellowship at the New York University Bellevue Medical Center. He later completed his pulmonary physiology fellowship at Johns Hopkins Medical School.
“I was immediately quite impressed by his intellect, absolute love for science, and his unwavering enthusiasm for the molecule VIP,” said Paul Hassoun, MD, a close friend and colleague of Sami’s. They first met at an ATS meeting, and the two men immediately bonded over their Middle Eastern heritage, “about which we were quite proud, a feeling mixed with worries, considering the endless turmoil in the region.”
| Sami pursued research in pulmonary medicine his entire career, and at the 2000 ATS International Conference he was named the Amberson Lecturer for his major contributions to the understanding of physiological and pathophysiological mechanisms involved in pulmonary vascular function. There he gave a talk on “Unraveling the Mysteries of Acute Lung Injury: Cell Death and Survival Pathways as Targets of Intervention.” |
Sami codiscovered the molecule vasoactive intestinal peptide (VIP) with colleague Viktor Mutt, PhD, at the Karolinska Institute in Stockholm, Sweden, and went on to publish several scientific papers on the topic. Devoted to an active career, Sami was never too busy to give advice and guidance to young investigators in the field.
“He was a true gentleman and always supportive of younger investigators,” says Nicholas S. Hill, MD, Professor of Medicine and Chief of the Pulmonary, Critical Care, and Sleep Division at Tufts University School of Medicine in Boston and former President of the ATS. Nicholas met Sami at an ATS conference 31 years ago when Sami congratulated him on his presentation. “He was always hoping to see the compound [VIP] commercialized for therapeutic use in pulmonary hypertension. Unfortunately, he never lived to see that hope realized.”
Sami will always be remembered for his contributions to the field of pulmonary circulation and widely respected for his research, which will continue to help develop novel therapeutic approaches for patients with pulmonary hypertension. He never retired.
Sami is survived by his sister, Nadia Behmann; his brother, Mufeed Said, MD; two nieces; and four nephews.
Dr. Sami Said's Obiturary
Google Patent Search for Dr. Said (14 Patents)
VIP Research Papers From ARDS to Cancer Link to Spreadsheet
Vasoactive Intestinal Peptide - Robert J. Henning, in Handbook of Biologically Active Peptides (Second Edition) 2013
2018 Shoemaker study:
Shoemaker application (https://www.fda.gov/media/102282/download)
the only mistake was that Schoemaker chose the wrong form of registration of the drug. There are arguably different forms of filing with the FDA. He chose the IRB instead of the IND proposal.
RLF-100™ is a synthetic form of Vasoactive Intestinal Peptide (VIP) consisting of 28 amino acids which was first discovered in 1970. Although initially identified in the intestinal tract, human VIP is now known to be produced throughout the body and to be primarily concentrated in the lungs. Here VIP has shown a multimodal mechanism of action: inhibition of viral replication, deterrence of inflammatory cytokines, prevention of cell death and upregulation of surfactant production. 70% of the VIP in the body is bound to a rare cell in the lung, the alveolar type 2 cell, which is critical to the transmission of oxygen to the body.
RLF-100™ has a 20-year history of safe use in humans in multiple human trials for sarcoidosis, pulmonary fibrosis, asthma/allergy, and pulmonary hypertension. It has been shown in more than 100 peer-reviewed studies to have potent anti-inflammatory/anti-cytokine activity in animal models of respiratory distress, acute lung injury and inflammation.
RLF-100™ is currently in clinical testing for acute lung injury (ALI) associated with the SARS-CoV-2 virus (COVID-19).
Cell Entry Mechanisms of SARS-CoV-2 Link
Oswald Cruz Foundation in Brazil Abstract
The neuropeptides VIP and PACAP inhibit SARS-CoV-2 replication in monocytes and lung epithelial cells, decrease the production of proinflammatory cytokines, and VIP levels are associated with survival in severe Covid-19 patients.
• Relief Therapeutics owns the patent to RLF100 and the process for synthesizing it.
• Relief Therapeutics has demonstrated some very very compelling results against COVID19
• RLF100 inhibits the virus from attaching to host cells in the lungs, AND…RLF100 Therapeutics prevents both Bradykinin and cytokine reducing inflammatory response before it begins, negating steroid use potentially
• Relief Therapeutics are already determined safe by the FDA.
• Relief Therapeutics intravenous RLF100 was submitted for EUA on 9/17 – awaiting FDA approval.
• Relief Therapeutics RLF100 clinical trials have reached the interim 102 patients on 9/30 – awaiting results.
• Relief Therapeutics clinical trial for the RLF100 treatment inhaler has been designed, submitted, and is expected to finish this year.
• Relief Therapeutics clinical trial for the RLF100 PREVENTATIVE inhaler has been designed, submitted, and is expected to finish next year.
• Relief Therapeutics show promise for other lung applications beyond Covid, which also need to be studied and tested separately
• Relief Therapeutics signed a Cooperative Agreement with NIH’s Institute of Arthritis and Infectious Diseases to test RLF-100 against the flu virus and other viruses that attack the lungs.
• Relief Therapeutics signed a contract with Bachem Americas to manufacture drug substance for 1 million patients.
• Relief Therapeutics signed a contract with Nephron Pharma to manufacture enough RLF100 for 1 million patients.
• Relief Therapeutics signed a contract with the largest supplier of inhaled sterile drugs in the United States to supply RLF-100 to any US hospital overnight.
• Relief Therapeutics obtained Companionate Care Protocol in Israel and we’re in the process of determining how to service it.
• NeuroRX’s CEO Dr. Javitt is ranked among the top 1% of quoted scientists worldwide, has successfully taken 7 drugs through the FDA process, and has served in key leadership roles under presidents Clinton, Bush Jr, Bush Sr, and Reagan.
• NeuroRX’s Chief of Operations, Robert Bestoff spent his career at Lilly & Pfizer. At Pfizer, he was head of the entire neuro science and pain division, responsible for $10B of their drugs.
• NeuroRX’s Manufacturing Coordinator, Rich Siegel, is the former head of Johnson & Johnson’s drug portfolio
Relief Therapeutics is a small Swiss company with a patent for a drug called RLF-100 that treats Covid-19 patients. RLF-100 is a safe, synthetic version of a naturally-occurring peptide in the human body.
Relief Therapeutics has partnered with NeuroRX (led by CEO Dr. Javitt) for assistance with the U.S. FDA process, as well as manufacturing and distribution within the United States, Canada and Israel. Operations for the rest of the world will be handled separately by Relief Therapeutics.
RLF-100 has 4 clinical trials underway, and initial results look exceptionally promising. Highlights are provided below.
AVIPTADIL RLF-100 VIP
• VIP (vasoactive intestinal polypeptide) is a naturally occurring peptide in the human body.
• Aviptadil is a VIP for the treatment of erectile dysfunction, proven to be safe since 1970’s.
• Aviptadil is being repurposed as RLF-100 to treat Covid-19 patients.
• RLF-100 is a safe, patented, synthetic form of VIP, which increases surfactant production in the lungs to protect against Covid-19.
• RLF-100 is a trifecta treatment: 1) It blocks Covid-19 from attaching to host cells in the lungs; 2) it prevents the cytokine storm; and 3) it reduces inflammation.
• RLF-100 has 4 separate clinical trials for intravenous and inhaler versions of the drug.
• RLF-100 is inexpensive and easy to manufacture.
• RLF-100 shows promise for other lung applications beyond Covid, which also need to be studied and tested separately.
STOCK / COMPANY
• Relief Therapeutics is a small company in Switzerland that holds the patent on RLF-100.
• Relief is traded over the counter (OTC) on the Swiss SIX exchange.
• In August 2020, Relief up-listed from “OTC Pink” to the higher-tier “OTCQB” to allow a broader range of investors. Relief intends to seek a future presence on the NASDAQ or NYSE.
• Relief has CHF $48M cash on hand ($52M USD), enough to support planned trials and operations through 2022, without taking into account any RLF-100 revenue.
• NeuroRX is a private US-based partner and has connections at the highest levels of government and big pharma. They are guiding Relief Therapeutics through the FDA approval process and organizing manufacturing and distribution.
• Relief and NeuroRX will split profits from sales: 50/50 for U.S., Canada and Israel, 85/15 (in favor of Relief) in Europe, and 80/20 (in favor of Relief) in all other territories.
Leadership Team: https://investorshub.advfn.com/boards/read_msg.aspx?message_id=158200526
Partnership Agreement: https://relieftherapeutics.com/relief-and-neurorx-announce-partnership-for-global-commercialization-of-rlf-100-and-selection-of-commercial-partners/
OTCQB Uplisting: https://relieftherapeutics.com/relief-announces-successful-up-listing-from-otc-pink-to-otcqb-and-capital-increase-from-its-share-subscription-facility-with-gem/
MANUFACTURING & DISTRIBUTION
• Robert Bestoff is the Chief of Operations and spent his career at Lilly & Pfizer. At Pfizer, he was head of the entire neuro science and pain division, responsible for $10B of drugs.
• Rich Siegel, former head of Johnson & Johnson’s drug portfolio, put together the manufacturing program.
• NeuroRX has signed 3 contracts in preparation to treat up to 1 million patients:
1) Bachem Americas has been contracted to manufacture drug substance for RLF-100.
2) Nephron Pharmaceuticals has been contracted to manufacture commercial supplies of RLF-100.
3) The largest supplier of inhaled sterile drugs in the United States, able to supply RLF-100 to any US hospital overnight, has been contracted as the pharmaceutical logistics partner.
M&D Contracts: https://relieftherapeutics.com/neurorx-and-relief-therapeutics-establish-supply-and-distribution-agreements-for-rlf-100-aviptadil-2/
2020-08-26 "Our Expanded Access Program is being managed by Clinigen."
- Prestige World Wide! Wide ...Wide..Wide...
2020-08-25 OTCQB Certification
- Exchange Uplisting
2020-08-25 Relief theraputics lists GEM's NYC office as their NYC office
2020-08-20 RLF-100 (Aviptadil) Intermediate Population Expanded Access Protocol (SAMICARE)
2020-08-20 Rapid Recovery from COVID-19 Respiratory Failure with Comorbidity in 21 Patients Treated with Vasoactive Intestinal Peptide
- BARDA in Title field of PDF document properties
- First 21 consecutive emergency access patients responded well
- Research support was provided by the Cavendish Impact Foundation and Princeton Alumni Angels.
- Clinical trial funding was provided by Relief Therapeutics Holdings, AG, Geneva and NeuroRx, Inc.
2020-08-12 Dr Yo: Discussion with Dr. Jonathan Javitt about Aviptadil and Vasoactive Intestinal Peptide
2020-08-06 FDA grants inhaled use IND for RLF-100 (aviptadil) to treat patients with moderate and severe COVID-19 aiming to prevent progression to respiratory failure
- Aerosolized Study Approved
2020-08-06 Some Nurse on youtube commenting about COVID
- She comments and gives her take aways
2020-08-03 RLF-100 (aviptadil) clinical trial showed rapid recovery from respiratory failure and inhibition of coronavirus replication in human lung cells
- Report on first 6 expanded use patients that were too sick to particpate in trial
- 5 of 6 emergency access patients showed rapid improvement and discharged though all intubated and recieving ECMO initially
2020-07-25 Vasoactive Intestinal Peptide treats Respiratory Failure in COVID-19 by rescuing the Alveolar Type II cell
- "Clinical reports are now emerging which document rapid recovery from Critical COVID-19 with respiratory failure within days of administering intravenous RLF-100"
|Corporate Contact |
RELIEF THERAPEUTICS Holding AG
Avenue de Sécheron 15
|Media Contact |
Anne Hennecke / Brittney Sojeva
MC Services AG
Phone: +49 (0) 211-529-252-14
FROM Page 1: RLFTF - OTCQB Listing Certification - Date August 18, 2020
2020 Half Year Report Relief Therapeutics
Published 9/15/2020 Auditor’s Mazars
2019 Annual Report
2018 Annual Report
2017 Annual Reoprt
RLFTF Share information from OTCBQ Certification Plus New Issues
|Shares Authorized || (A) ||4,458,998,544 |
|Total Shares Outstanding || (B) ||2,383,168,581 |
|Number of Restricted Shares || (C) ||0 |
|Unrestricted Shares Held by Officers, Directors, 10% Contro l Persons & Affiliates || (D) ||906,359,296 |
|Public Float: Subtract Lines C and D from Line B || (E) ||1,476,809,285 |
|% Public Float: Line E Divided by Line B (as a %) || (F) ||62.0% |
|Number of Beneficial Shareholders of at least 100 shares || (G) ||7209 |
|Current Market Capitalization @ $0.58 per Share || ||$1,382,237,777 |
|2020-09-28 Relief Announces Capital Increase from its Final Tranche of the Share Subscription Facility with GEM || ||196,900,000 |
|Current Total OS Shares || ||2,580,068,581 |
FROM Page 3: RLFTF - OTCQB Listing Certification - Date August 18, 2020
|Name ||Shares Owned ||Options |
(converted in 60 days)
(converted in 60 days)
|% of Class of shares owned |
|GEM Global Yield Fund LLC SCS |
Christopher Brown, New York
|730,744,258 || ||666,658,667 ||30.66% |
|Yves Sagot ||164,626,313 ||10,000,000 || ||6.91% |
|Thomaz Burckhardt ||10,845,725 || || ||0.46% |
|Jeremy Meinen ||143,000 || || ||0.01% |
| TOTALS ||906,359,296 ||10,000,000 ||666,658,667 ||38.03% |
Relief Insider Trades
9/17/2020 Gael Hedou Purchased Shares 16,375,998
RLF AG teams up with NeuroRX
Videos, Conferences & Webcasts 10/15/2020 Solebury Trout Video with Transcript https://sites.google.com/view/aguyus
Dr. Javitt’s on various webcast with & Transcripts downloadable
9/30/2020 Javiit on Dr Yo Video with Transcript https://sites.google.com/view/aguyus
8/12/2020 Javiit on Dr Yo Video with Transcript https://sites.google.com/view/aguyus
RLF-100 Intellectual Property
Public Term Search Links
Google News: RLF-100,RLFTF
Google Trends: RLF-100,RLFTF
"Relief Therapeutics holds FDA orphan drug designations for the use of VIP to treat ARDS, pulmonary hypertension, and sarcoidosis."
"On 28 August 2006, orphan designation (EU/3/06/395) was granted by the European Commission to mondoBIOTECH Laboratories, Lichtenstein, for Aviptadil for the treatment of acute lung injury."
RLF AG realized what they had might be beneficial to COVID ARDS treatment
RLF AG teams up with a NeuroRx
US IV Trial
Paper on 21 CONSECUTIVE emergency use IND patients (too sick for IV trial)
Vasoactive Intestinal Peptide has demonstrated an immediate clinical response in some patients with COVID-19 respiratory failure. A response of this magnitude has previously not been seen with an antiviral agent and is akin to the first reports of penicillin in treating pneumococcal pneumonia. Similar results have been demonstrated in acute respiratory distress syndrome caused by sepsis."
Initial EAP Results Pre-print: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3665228
ONGOING CLINICAL TRIALS
Relief has the following 4 clinical trials underway:
Link to all 4 trials: https://clinicaltrials.gov/ct2/results?term=Aviptadil&draw=2&rank=1#rowId0
1) Clinical Trial NCT04311697 – IV Trial
• This trial is for intravenous RLF-100 administered to patients in ICUs with respiratory failure.
• The trial seeks to enroll 144 patients.
• The trial is currently in “Phase 2b/3”, meaning it will evaluate both dosing and efficacy.
• A first interim review was held at 30 patients, which determined RLF-100 is safe for human use.
• A second interim review will be held at 102 patients with a determination to: 1) stop the trial because the drug is dangerous, 2) stop the trial because the drug shows no effect, 3) continue the trial because results look good, 4) stop the trial because the drug is proven.
• Patient #102 was enrolled on 9/30/2020; therefore once that patient completes their trial (28 days later), the Data Monitoring Committee (DMC) will review results and submit a recommendation to the FDA.
• Doctor (and Congressman) Andy Harris is 1 of 3 experts on the DMC.
First Interim Review: https://relieftherapeutics.com/neurorx-and-relief-therapeutics-announce-data-monitoring-committee-determination-to-continue-phase-2-3-trial-of-rlf-100-for-critical-covid-19/
2) Clinical Trial NCT04453839 – EAP Trial
• This EAP (Expanded Access Protocol) trial allows RLF-100 to be used as a last-resort for patients too sick for regular trial participation (commonly referred to as "compassionate use").
• EAP is NOT the same as EUA (Emergency Use Authorization) – see clarification below
• Early EAP results were released in a “pre-print” document for patients considered to be “the sickest of the sick” (ICU, ventilator, ECMO patients).
• Results: For patients who received RLF-100, 19 out of 21 patients survived, where only about 6 were expected to survive.
Initial EAP Results Pre-print: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3665228
Clarification: EAP and EUA
• EAP = Expanded Access Protocol – currently approved
• EUA = Emergency Use Authorization – submitted application to FDA
• EAP allows RLF-100 to be used as a last-resort for patients too sick for regular trial participation.
• Qualifying for EAP is limited: the patient must be located at one of the few clinical trial hospitals, or transfer to a participating hospital, or have the hospital attempt to qualify for the drug.
• Due to EAP limitations, NeuroRX recently applied for EUA and is awaiting FDA approval.
• EUA allows experimental drug use during public health emergencies. Qualifications are that the drug must be safe and “may” be effective.
• If approved, EUA will allow RLF-100 to be used at all US hospitals, as a last resort when all other approved treatments have failed.
• EUA approval is not necessarily dependent upon trial completion or interim reviews, unless FDA subsequently requests more data.
• Currently there are only 2 other EUA approved therapeutics: Remdesivir and Convalescent Plasma.
2020-09-17 EUA Submittal: https://relieftherapeutics.com/relief-partner-neurorx-submits-request-for-emergency-use-authorization-for-rlf-100-aviptadil-in-the-treatment-of-patients-with-critical-covid-19-and-respiratory-failure-who-have-exhausted-a/
Other Approved EUAs: https://www.fda.gov/media/136832/download
3) Clinical Trial NCT04360096 – Treatment Inhaler
• This trial is a study of 288 patients in the United States to test an inhaler-version of RLF-100, intended to ultimately be used for in-home nebulizer treatments.
• Dr. Javitt: “We expect that half the people we enroll in our inhaled study are going to be people who are outpatients.”
• Current estimated completion in 2020
Side By Side
4) Clinical Trial NCT04536350 – Preventative Inhaler
• This trial is a study of 80 patients in Switzerland to test an inhaler-version of RLF-100 as a “preventative treatment”.
• Current estimated completion in December 2021
• Signed a cooperative agreement with NIH’s Institute of Arthritis and Infectious Diseases to test RLF-100 “against the flu virus and other viruses that kill people by attacking the lungs.”
• Israel has already granted Companionate Care Protocol across the country, and NeuroRX is in the process of determining how to serve it.
• When asked whether FDA approval would have an impact on other countries, Dr. Javitt responded with “the FDA determinations are highly influential around the globe”.
History Dr. Said->Stony Brook->Mondo Biotech->Therametrics->Relief AG
RLF-100, was acquired by RELIEF THERAPEUTICS Holding SA (Swiss Exchange: RLF, OTCBB: RLFTF) from the business combination of RELIEF THERAPEUTICS Holding SA and Therametrics Holding AG in January 2016. THERAMetrics holding AG formerly was known as MondoBIOTECH holding AG.
10 Orphan Drugs in EU and US
19 Patents Granted
81 medicinal Products candidates
22 patent Families filed
312 Peptides to Redirect in Rare disease
Mondo Biotech Patents
6/20/2013 MondoBiotech holding AG changes name Therametrics Holding AG
“ The company changed its name from mondoBIOTECH holding AG to THERAMetrics holding AG as at 20 June 2013”
Notes to the Financial Statements see 1. General Information Page 7