Capsaicin

- Supera-CBD eased heat-related pain due to inflammation quickly and provided long-lasting pain relief lasting up to five hours - Results suggest Supera-CBD may target specific pain pathways, lessening the potential for side effects - MyMD was issued Japanese Patent No. 7293561 B2, covering Supera-CBD as a new molecular entity, in pharmaceutical formulations, and for use in therapeutic treatments BALTIMORE--(BUSINESS WIRE)-- MyMD Pharmaceuticals, Inc.® (Nasdaq: MYMD) (“MyMD” or “the Company”), a clinical stage biopharmaceutical company developing groundbreaking therapies for the treatment of serious and debilitating autoimmune and inflammatory diseases, today announced results from a preclinical study of its investigational cannabinoid Supera-CBD™, a novel, synthetic, non-toxic cannabidiol (CBD) analog. In the study, Supera-CBD targeted and quickly reduced inflammatory pain within 60 minutes, providing pain relief for up to five hours. Comparatively, traditional CBD had no effect on this type of pain in the same study. “These preclinical results illustrate the potential of Supera-CBD to alleviate acute inflammatory pain related to injuries, burns, surgery, and flare-ups from chronic inflammatory conditions such as diabetic neuropathy and shingles,” said Chris Chapman, MD, president, director and chief medical officer, MyMD. “Moreover, these are exciting findings in that the effect demonstrated appears to be targeted, as Supera-CBD alleviated pain due to heat but did not affect pain related to touch in the model of inflammation. This may indicate the potential for fewer side effects compared to traditional opioid pain treatments, without the functional impairment due to numbness in affected areas.” According to study researchers at a major academic center where the study was conducted, the results indicate that Supera-CBD may have an effect on the body’s TRPV1 pain system channels, which control heat-related pain.1 Added Dr. Chapman, “By targeting the TRPV1 channels, which these results indicate Supera-CBD may be capable of, we have the potential to advance treatment in inflammatory-related pain, an area of great patient need.” Dr. Chapman also noted that it was very significant that the “U.S. Department of Justice Drug Enforcement Administration (DEA)’s scientific review concluded Supera-CBD will not be considered a controlled substance or listed chemical under the Controlled Substances Act (CSA) and its governing regulations or require scheduling during development.” Acute pain related to inflammation, burns, and nerve-related pain affects countless individuals worldwide. The global market for pain management was valued at around $36 billion in 2021 and is expected to reach $52 billion by 2026. About Supera-CBD Supera-CBD™ is a synthetic, non-toxic cannabidiol (CBD) analog that is an 8000-times more potent CB2 agonist than plant-based CBD. In addition to its potential role in managing addiction, anxiety, chronic pain and seizures, Supera-CBD has also been shown in preclinical studies to have anti-inflammatory effects. Supera-CBD is a unique synthetic analog of CBD whose structure has been modified to be CB2-receptor selective. Studies to investigate Supera-CBD’s binding and affinity to CB1 and CB2 receptors show that the compound had very low affinity to CB1 and had a four-fold increase in binding to the CB2 receptor in comparison to CBD. Supera-CBD has completed genotoxicity studies, and the company has initiated preclinical pain studies in partnership with Johns Hopkins Medicine. On June 20, 2023, MyMD was issued Japanese Patent No. 7293561 B2, covering Supera-CBD™ as a new molecular entity, in pharmaceutical formulations, and for use in therapeutic treatments. With this latest issuance, the Company now has 23 issued patents worldwide protecting this drug product candidate, along with two pending applications. About MyMD Pharmaceuticals MyMD Pharmaceuticals, Inc. (Nasdaq: MYMD), is a clinical stage biopharma company developing groundbreaking therapies for the treatment of serious and debilitating autoimmune and inflammatory diseases. MyMD’s lead clinical candidate, MYMD-1®, is an orally available next-generation TNF-α inhibitor with the potential to transform the way that TNF-α based diseases are treated. MYMD-1®, with its small molecule design, improved safety pro ability to cross the blood brain barrier, has the promise to provide meaningful therapeutic solutions to patients not served by current TNF-α inhibitors and as a potential therapy for CNS-based inflammatory and autoimmune diseases. The company has completed Phase 2 studies of MYMD-1® for sarcopenia/frailty, a result of the aging process, as well as early-stage trials for rheumatoid arthritis (RA), with the potential to expand into other applications. MyMD’s second therapeutic candidate is Supera-CBD, a novel, synthetic, non-toxic cannabidiol (CBD) analog that is 8000 times more potent a CB2 agonist (activator) than plant-based CBD. In addition to its potential role in managing addiction, anxiety, chronic pain and seizures, Supera-CBD has also been shown to have anti-inflammatory effects. For more information, visit . Cautionary Statement Regarding Forward-Looking Statements This press release may contain forward-looking statements. These forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause actual results, performance, or achievements to be materially different from any expected future results, performance, or achievements. Forward-looking statements speak only as of the date they are made and none of MyMD nor its affiliates assume any duty to update forward-looking statements. Words such as “anticipate,” “believe,” “could,” “estimate,” “expect,” “may,” “plan,” “will,” “would’’ and other similar expressions are intended to identify these forward-looking statements. Important factors that could cause actual results to differ materially from those indicated by such forward-looking statements include, without limitation: the timing of, and MyMD’s ability to, obtain and maintain regulatory approvals for clinical trials of MyMD’s pharmaceutical candidates; the timing and results of MyMD’s planned clinical trials for its pharmaceutical candidates; the amount of funds MyMD requires for its pharmaceutical candidates; increased levels of competition; changes in political, economic or regulatory conditions generally and in the markets in which MyMD operates; MyMD’s ability to retain and attract senior management and other key employees; MyMD’s ability to quickly and effectively respond to new technological developments; MyMD’s ability to protect its trade secrets or other proprietary rights, operate without infringing upon the proprietary rights of others and prevent others from infringing on MyMD’s proprietary rights; and the impact of the COVID-19 pandemic or similar public health emergencies on MyMD’s results of operations, business plan and the global economy. A discussion of these and other factors with respect to MyMD is set forth in the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, filed by MyMD on March 31, 2023, as may be supplemented or amended by the Company’s Quarterly Reports on Form 10-Q. Forward-looking statements speak only as of the date they are made and MyMD disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise. 1 Reference: TRPV1 is a non-selective cation channel; when it is activated by capsaicin, sodium and calcium ions flowing through TRPV1 into the cell to depolarize nociceptive neurons, leading to action potential firing and finally the sensation of spiciness (Caterina et al., 1997).

All study objectives were met, demonstrating safety across dose groups and confirming efficacy and durability at the selected doses against placebo (lidocaine) and active control (steroid). All RTX doses (7.5 to 20 µg) were well-tolerated, with few severe or serious adverse events (AEs). The majority of reported AEs related to pain post-administration and resolved within hours following treatment. Very few severe AEs were reported across groups (including placebo) with no dose correlation. RTX post-injection administration pain was easily controlled. RTX 20mcg dose outperformed all other dose groups (including the approved drug for this indication (intra-articular corticosteroids)) for efficacy and durability at and beyond 26 weeks post-treatment. RTX 20mcg and 12.5mcg have been selected as the clinically optimal and minimally effective doses for further phase 2 pivotal or phase 3 trials. SAN DIEGO, Sept. 07, 2023 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (OTC: SRNEQ, "Sorrento") announced today positive Phase 2a top-line clinical trial results for the RTX program. The Phase 2a study follows the positive observations from the Phase 1b/2 trial results (NCT03542838) of RTX Day 84 patient data, for which Sorrento has completed the one-year follow up for the last patient dosed in February 2021. The phase 2 trial, a multi-center, double blind, placebo- and active-controlled study, assessed the efficacy and safety of several dose groups of RTX to manage pain in patients with moderate-to-severe OAK (clinicaltrials.gov: NCT04885972). Given the durability of OAK pain relief response to RTX demonstrated in earlier phase 1b/2 trials, Sorrento decided to include an active approved comparator (Zilretta® intra-articular corticosteroids) in the current trial protocol. Top-Line Safety Outcomes (Summary) Generally, treatment was well-tolerated, with the most common noted AE being pain following topical capsaicin 0.1% given to all patients for blinding purposes and study drug administration in the knee (across all dose groups). Very few serious AEs were noted across all dose groups, with one in particular (see below for additional detail) in the 15mcg RTX group being severe/life threatening (hypertension following drug administration), which resolved within hours with treatment of pain and no additional intervention. In the cases requiring pain control (any group) the dose of opioid was comparable. A few subjects in RTX groups required use of low dose oral opioids for up to 6 hours in some cases of prolonged moderate discomfort/pain. No patient required additional pain control or intervention after 6 hours or in the days following the day of administration and no patient left the clinic with opioids or an opioid prescription. A table accompanying this announcement is available at Subject 008-005, a 55-year-old female with a prior history of hypertension (HTN) and morbid obesity (BMI 46.9) developed elevated blood pressure about fourteen minutes post-RTX dose (208/147), which coincided with severe pain. The subject received hydromorphone 0.8 and 0.4 mg IV and then oxycodone 5 mg twice, and the HTN resolved without any other intervention. The HTN did not recur, and the subject’s ECG was normal. Discharge blood pressure was 140/74. Sponsor’s medical monitor disagreed with the characterization as life-threatening or an SAE as the clinic stay was not prolonged and the HTN required no treatment other than treating the subject’s pain. Sponsor also felt that the AE should have been considered a related event (marked unrelated by investigator). Top Line Efficacy and Durability Outcomes (Summary) The RTX 20mcg dose group performed best among all dose groups, including placebo (lidocaine only) and approved intra-articular corticosteroid (Zilretta) on short-term and prolonged pain relief measures (SPID, KOOS, WOMAC). Summary of Pain Intensity Difference (SPID) A chart accompanying this announcement is available at Although at many time points, RTX 20mcg was statistically significant as compared to the approved drug (Zilretta®) in this indication active control, we note that the study was not powered to demonstrate statistical significance for all end points listed (primary, secondary), with only 120 patients enrolled across 5 RTX dose groups and early terminations due to the Company’s previously announced bankruptcy proceedings. Despite the limitations of the study (small number of patients per group, high variability of placebo responders due to intra-articular use of 10ml lidocaine and capsaicin cream for blinding per FDA request), the results = demonstrate that RTX 20mcg is an effective pain treatment for longer durations (up to one year), with better score improvements at week 26 and 52 than the current standard of care (active steroid injection. Zilretta) up to and past week 26. A chart accompanying this announcement is available at A higher proportion of patients responded to treatment with RTX 20mcg than any other treatment group, including Zilretta. Reduction in pain was also more pronounced with RTX 20mcg than with any other treatment group, including placebo and active control. A table accompanying this announcement is available at Durability of treatment was nearly twice as long for RTX 20mcg than active steroid control (mean time to return to 10% of baseline of 19 weeks for RTX versus 10 weeks for Zilretta). In conclusion, we report that the phase 2a OAK study for RTX has met all the primary and secondary objectives for the study. The Phase 2a results were consistent with the prior safety pro the drug from the previously completed Phase 1 study and has allowed for the potential determination of a therapeutically effective dose for further phase 2 pivotal or phase 3 studies, which is expected to be powered with a sufficient number of patients to provide significantly different results from the controls. “We are extremely pleased with the outcome of this study. The clinical trial confirmed the potential of resiniferatoxin (RTX) in helping patients with moderate to severe osteoarthritis pain for at least 6 months, if not longer. No other drug on the market can provide this much pain relief, for this long a period, from a single administration,” stated Dr. Henry Ji, Chairman and Chief Executive Officer. About RTX A thousand times “hotter” than pure capsaicin (16 billion Scoville units versus 16 million), and with a high affinity for afferent sensory pain nerves, RTX binds to TRPV1 receptors present and selectively ablates the nerve endings responsible for pain signals experienced by patients1. Delivered peripherally (into the joint space) the transient nerve ending ablation effect can have profound clinical benefits lasting for months to years (as shown in canine studies2). The first arthritis pain clinical trial in humans was completed in 2021. That study was a multicenter, placebo-controlled Phase 1b/2 study to assess the safety and define the maximally tolerated dose of RTX administered in the knee joint in patients with moderate to severe pain associated with osteoarthritis of the knee. The study was a dose-escalation trial in which cohorts of patients receive increasing doses of RTX until the maximum tolerated dose (MTD) was achieved. The primary objective of the study was to evaluate the safety of RTX and identify the recommended Phase 3 dose. The secondary objective was to assess the preliminary efficacy of RTX measured by assessing changes in the intensity of pain using the A1 score from the WOMAC, a widely used proprietary validated pain questionnaire. The second arthritis pain phase 2a clinical trial in humans completed enrollment in September 2022. The results of study are expected to confirm the phase 3 doses and demonstrate long-term effectiveness of RTX in controlling osteoarthritis pain when compared to placebo or active steroid intra-articular injections. Sorrento continues to progress as planned on all clinical fronts of the RTX program, including exploring additional orphan indications with breakthrough potential. RTX is an extremely potent compound used therapeutically in very small concentrations. It is very challenging to formulate and keep stable long-term when made in large quantities. Sorrento has been working on process optimization of RTX manufacturing for several years and continues to advance the validation and scale up, with the expectation to have final validated batches completed by the end of 2023. Ensuring the company can meet market demands from API to finished product once phase 3 trials have been completed has been identified as a critical priority, which Sorrento is currently addressing. The osteoarthritis treatment market and in particular the Knee Osteoarthritis and injectable markets have historically seen healthy growth and are expected to continue the trend as populations age and present excessive weight. More information on this completed trial can be found at (NCT03542838). About Sorrento Therapeutics, Inc. Sorrento is a clinical and commercial stage biopharmaceutical company developing new therapies to treat cancer, pain (non-opioid treatments), autoimmune disease and COVID-19. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as next-generation tyrosine kinase inhibitors (“TKIs”), fully human antibodies (“G-MAB™ library”), immuno-cellular therapies (“DAR-T™”), antibody-drug conjugates (“ADCs”), and oncolytic virus (“Seprehvec™”). Sorrento is also developing potential antiviral therapies and vaccines against coronaviruses, including STI-1558, COVISHIELD™ and COVI-MSC™; and diagnostic test solutions, including COVIMARK™. Sorrento’s commitment to life-enhancing therapies for patients is also demonstrated by our effort to advance a TRPV1 agonist non-opioid pain management small molecule, resiniferatoxin (“RTX”), and SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (SEMDEXA™), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, and to commercialize ZTlido® (lidocaine topical system) 1.8% for the treatment of postherpetic neuralgia (PHN). RTX has been cleared for a Phase II trial for intractable pain associated with cancer and a Phase II trial in osteoarthritis patients. Positive final results from the Phase III Pivotal Trial C.L.E.A.R. Program for SEMDEXA™, its novel, non-opioid product for the treatment of lumbosacral radicular pain (sciatica), were announced in March 2022. ZTlido® was approved by the FDA on February 28, 2018. For more information visit . Forward-Looking Statements This press release and any statements made for and during any presentation or meeting contain forward-looking statements related to Sorrento Therapeutics, Inc., under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding the expectations for Sorrento's and its subsidiaries' technologies and product candidates, including, but not limited to, resiniferatoxin (RTX), the clinical potential of RTX, including the potential for RTX to address long-term control of pain associated with osteoarthritis of the knee, RTX’s potential to become a key therapeutic in the knee osteoarthritis and injectable markets, expected timing of initial efficacy data on pain relief parameters and initial topline data, the potential superiority of RTX over any active comparators, timing for conducting an end of phase 2 meeting with the FDA and concurrent phase 3 clinical trials, completion and submission of a request to proceed with any Phase 3 trial for RTX, the possibility of proceeding to a Phase 3 trial, the possibility of obtaining accelerated international registration for RTX, any potential additional orphan indications for RTX with breakthrough potential and the expected timing for having final validated batches for RTX. Risks and uncertainties that could cause our actual results to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: risks related to Sorrento's technologies and prospects, including, but not limited to risks related to seeking regulatory approval for RTX; clinical development risks, including risks in the progress, timing, cost, and results of clinical trials and product development programs; risk of difficulties or delays in obtaining regulatory approvals; risks that clinical study results may not meet any or all endpoints of a clinical study and that any data generated from such studies may not support a regulatory submission or approval; risks that prior test, study and trial results may not be replicated in continuing or future studies and trials; risks of manufacturing and supplying drug product; risks related to leveraging the expertise of its employees, subsidiaries, affiliates and partners to assist Sorrento in the execution of its product candidates strategies; risks related to the global impact of COVID-19; risks relating to the voluntary proceedings under Chapter 11 in the Bankruptcy Court (the “Chapter 11 Cases”), Sorrento’s ability to continue operating in the ordinary course while the Chapter 11 Cases are pending, the timing and outcome of the Chapter 11 Cases, Sorrento’s ability to obtain timely approval by the Bankruptcy Court of the motions filed in the Chapter 11 Cases, employee attrition and Sorrento’s ability to retain senior management and other key personnel due to the distractions and uncertainties of the Chapter 11 Cases, Sorrento’s ability to maintain relationships with suppliers, customers, employees and other third parties and regulatory authorities as a result of the Chapter 11 Cases, the Bankruptcy Court’s rulings in the Chapter 11 Cases, the length of time that Sorrento will operate under Chapter 11 protection and the continued availability to Sorrento of operating capital during the pendency of the Chapter 11 Cases, risks associated with any third party motions in the Chapter 11 Cases, increased administrative and legal costs related to the Chapter 11 process, exposure to potential litigation and inherent risks involved in a bankruptcy process, the potential adverse effects of the Chapter 11 Cases on Sorrento’s liquidity or results of operations, or Sorrento’s ability to timely periodic reports or meet periodic reporting requirements with the SEC; and other risks that are described in Sorrento's most recent periodic reports filed with the Securities and Exchange Commission, including Sorrento's Annual Report on Form 10-K for the year ended December 31, 2022, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and we undertake no obligation to update any forward-looking statement in this press release except as required by law. Media and Investor Relations Contact Alexis Nahama, DVM (Head of RTX Program) Email: mediarelations@sorrentotherapeutics.com Sorrento® and the Sorrento logo are registered trademarks of Sorrento Therapeutics, Inc. G-MAB™, DAR-T™, Seprehvec™, SOFUSA™, COVISHIELD™, COVIDROPS™, COVI-MSC™, COVIMARK™ and Fujovee™ are trademarks of Sorrento Therapeutics, Inc. SEMDEXA™ is a trademark of Semnur Pharmaceuticals, Inc. A proprietary name review by the FDA is planned. ZTlido® is a registered trademark owned by Scilex Pharmaceuticals Inc. All other trademarks are the property of their respective owners. ©2023 Sorrento Therapeutics, Inc. All Rights Reserved. ________________________ 1 2 Sorrento Therapeutics (Ark Animal Health) internal data (on file) Table 1 Table 1 Chart 1 Chart 1 Chart 2 Chart 2 Table 2 Table 2