Sorrento Releases Positive Results of Phase 1B Trial of Resiniferatoxin (RTX) In Reduction of OsteoArthritis (OA) Knee Pain

• Phase 1b safety data at 6 month post-administration and Day 84 efficacy data available for all patients enrolled.
  
• No dose limiting toxicities at any of the doses tested (up to 30 ug) at 6 months post-administration. The study is scheduled to complete the last patient follow-up (1 year) in 1Q2021.
  
• Dose of 12.5ug selected as the likely optimal intra-articular therapeutic dose for future clinical trials. Durable signal at 12 weeks post-injection justifies initiation of Phase 2 (dose confirmation against active drug and saline control).
  
• Pain control in patients with advanced disease (Kellgren-Lawrence grade 3/4) show persistence of relief beyond 6 months and composite WOMAC A+C suggests that RTX could be a promising alternative for control of refractory pain in patients candidates for elective joint replacement.

SAN DIEGO, Sept. 28, 2020 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (NASDAQ: SRNE, "Sorrento") released positive Phase 1b trial data (clinicaltrials.gov NCT03542838) of resiniferatoxin (RTX) with completed Day 84 effectiveness data (end-point analysis) for all patients and completed six-month follow-ups in all doses for all patients enrolled, with no negative safety signal as of September 2020.

Dr. David Leiman, MD, a board certified anesthesiologist, Clinical Assistant Professor of Surgery, University of Texas at Houston, Director of Chronic Pain at Lotus Clinical Research in Houston, Texas and lead investigator for this clinical trial, commented, “RTX is a promising new treatment that fits a clear unmet need for osteoarthritis patients, particularly when traditional pain management options are insufficient or come with significant drawbacks such as those encountered with opioids. After participating in this trial and interacting with treated patients, I am looking forward to the day RTX might be approved as it would be another much needed tool in my specialty to help address difficult to control pain.”

The Phase 1b trial was a placebo controlled ascending dose study with an open-label extension to assess the safety and preliminary efficacy of intra-articular administration of RTX or saline control (as placebo group) for the treatment of moderate to severe pain due to osteoarthritis (OA) of the knee. It was expanded into a dose confirmation cohort to validate the safety and efficacy of the selected therapeutic dose compared to the individual’s baseline.

An abstract presenting intermediate data was accepted for the OsteoArthritis Research Society International (OARSI) meeting which was to be held in May 2020. The meeting was cancelled due to COVID-19 restrictions. The abstract has now been released from embargo and can be accessed on the conference website (OARSI Conference Posters) under #197 on page S138.

These strong results have prompted the Company to rapidly advance the investigational drug product into a Phase 2 clinical trial (against active drug and saline control) expected to start in 2020 and a subsequent Phase 3 clinical trial expected to start in 2021 after completing additional enabling preclinical studies.

Updated Safety Outcome (primary end-point)

Ten subjects received a single saline-control injection and 84 subjects received a single RTX injection. The majority of subjects (N=50) were dosed with resiniferatoxin at 12.5 µg. No dose limiting toxicities were observed in any of the 84 subjects dosed with RTX at any dose level studied.

Treatment-emergent adverse events (TEAEs) were expected based on the mechanism of action of the drug and included post-injection pain, tachycardia and hypertension; all of which resolved in less than a day. Mild to moderate post-procedural pain was reported as expected in nearly all subjects dosed with RTX (as well as in subjects treated with saline control) and was managed with analgesics. The pain from drug administration typically subsided within a few hours. No special requirements such as knee cooling or local anesthetics application have been used in this study.

Table 1:        Subjects with Treatment-Emergent Adverse Events in Study PTVA-OA-001

Updated Efficacy Outcomes (secondary end-point)

The magnitude of the difference in the treatment effect versus saline control (as placebo used in the ascending dose portion of the study) at 12 weeks exceeded what is traditionally considered sufficient to support regulatory approval based on greater than 2 points reduction in the WOMAC A1 10-point scale question “pain at walking on flat surface” compared to placebo.

In the RTX dose selected for upcoming clinical trials (12.5 ug), the WOMAC A1 score at day 84 showed an average of a 4.92-point reduction relative to baseline for RTX, and an average 2.59-point reduction relative to the saline control (placebo).

Fast relief (less than a week) and durability of the effect (over 84 days) confirm the clinical potential of the drug for long-term control of pain associated with OA of the knee.

The study was designed to follow patients to day 84. Patients were also given the option to be followed for a longer period of time. RTX treated patients with good initial response who were evaluated at day 168 showed pain relief to levels equivalent to their D84 response (likely persistence of effect).

Exploratory end-points: Advanced disease (Kellgreen-Lawrence Grade 3 and 4) and Womac A+C Composite Score

No difference in efficacy response was found regardless of the degree of measured OA in patients (Kellgren-Lawrence Grade 2, 3 or 4), suggesting that the strength and duration of pain relief observed following RTX treatment in this Phase 1b study may also be expected in a larger population of patients with advanced OA.

To confirm the potential of RTX to benefit patients waiting for total knee replacements, an analysis was performed applying a composite score (Womac A plus Womac C) that is traditionally used to assess a patients “qualification” for knee replacement (see Table 2).

Patients who could qualify for total knee replacement (Womac A + C over 23) showed a clear improvement following treatment (68% improved by at least 20%, versus 20% in the control group). The effect (see Figure 2) was sustained for at least 84 days with a signal that did not seem to degrade at day 84. Many patients followed through day 168 or day 365 indicate the potential of the drug effect to persist in responders for 6 months or more. These numbers, although encouraging, need to be confirmed in trials with a larger number of patients (such as Sorrento’s proposed Phase 2 and 3 trials).

Table 2:         Responder* Analysis at Day 84 (Week 12). Subjects with Baseline Combined WOMAC A Pain Subscale and WOMAC C Function Subscale >=23

* Responder defined as combined score for WOMAC A Pain Subscale and WOMAC C Function Subscale with at least a 20% decrease from baseline at Day 84 (Week 12). Note: Subjects without Day 84 data were included as Non-Responders.

Sorrento has confirmed it will be pursuing RTX for treatment of OA pain following a traditional development program, but based on the positive results of this Phase 1b trial will also add studies focusing on demonstrating the value of RTX as an alternative to TKR surgery.

About Resiniferatoxin (RTX)

A thousand times “hotter” than pure capsaicin (16 Billion Scoville units versus 16M), and with a high affinity for afferent sensory pain nerves, resiniferatoxin 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).

PTVA-OA-001 was a multicenter, placebo-controlled Phase 1b study to assess the safety and define the maximally tolerated dose of resiniferatoxin 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 received increasing doses of resiniferatoxin until the maximum tolerated dose (MTD) was achieved. The primary objective of the study was to evaluate the safety of resiniferatoxin and identify the recommended dose for Phase 3 trials. The secondary objective was to assess the preliminary efficacy of resiniferatoxin measured by assessing changes in the intensity of pain using the A1 score from the WOMAC Index, a widely used proprietary validated pain questionnaire.

More information on this trial can be found at www.clinicaltrials.gov (NCT03542838).

Information on upcoming Phase 3 trials (Total Knee Replacement Surgery Deferment Pain and Osteroarthritis Pain) can be found under the trial references NCT04386980 and NCT04044742.

About Sorrento Therapeutics, Inc. 

Sorrento is a clinical stage, antibody-centric, biopharmaceutical company developing new therapies to treat cancers. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as fully human antibodies (“G-MAB™ library”), clinical stage immuno-cellular therapies (“CAR-T”, “DAR-T”), antibody-drug conjugates (“ADCs”), and clinical stage oncolytic virus (“Seprehvir^®”, “Seprehvec™”). Sorrento is also developing potential antiviral therapies and vaccines against coronaviruses, including COVIDTRAP™, ACE-MAB™, COVI-MAB™, COVI-GUARD™, COVI-SHIELD™ and T-VIVA-19™; and diagnostic test solutions, including COVI-TRACK™ and COVI-TRACE™.

Sorrento's commitment to life-enhancing therapies for patients is also demonstrated by our effort to advance a first-in-class (TRPV1 agonist) non-opioid pain management small molecule, resiniferatoxin (“RTX”), and ZTlido^® (lidocaine topical system) 1.8% for the treatment of post-herpetic neuralgia. RTX has completed a Phase IB trial for intractable pain associated with cancer and is completing a Phase 1B trial in osteoarthritis patients. ZTlido^® was approved by the FDA on February 28, 2018.

For more information visit www.sorrentotherapeutics.com

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 potency, potential pain relief capabilities and potential duration of pain relief of RTX; the expected optima intra-articular therapeutic dose of RTX for future clinical trials; the safety and efficacy of RTX; the expected timing for the last visit for the last patient follow-up (1 year); the clinical potential of RTX; the ability of RTX to be an alternative pain management option for control of refactory pain; the expected commencement of any Phase 2 or Phase 3 trials for RTX; the completion of additional enabling preclinical studies; ; the potential impact of COVID-19 on elective surgeries, such as total knee replacement for OA knee pain and potential future studies focusing on demonstrating the value of RTX as an alternative to TKR surgery. 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 and its subsidiaries' technologies and prospects, including, but not limited to, RTX; risks related to seeking regulatory approvals and conducting and obtaining results of clinical trials, including, but not limited to, the PTVA-OA-001 study or trial and any prior RTX studies in animals; costs associated with RTX clinical trials; risks that prior test, study and trial results may not be replicated in future studies and trials; the clinical and commercial success of RTX; the viability and success of using RTX for treatments in certain therapeutic areas, including OA; risks related to the global impact of COVID-19; and 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, 2018, 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, SVP Corporate Development and Head of the RTX Program.

Telephone: 1.858.203.4120

Email: mediarelations@sorrentotherapeutics.com

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Sorrento^® and the Sorrento logo are registered trademarks of Sorrento Therapeutics, Inc. G-MAB™, COVI-GUARD™, COVI-SHIELD™, COVIDTRAP™, T-VIVA-19™, COVI-MAB™, ACE-MAB™, COVI-TRACK™, and COVI-TRACE™ are trademarks of Sorrento Therapeutics, Inc.

ZTlido^® is a trademark owned by Scilex Pharmaceuticals Inc.
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¹ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC398431/
² Sorrento Therapeutics (Ark Animal Health) internal data (on file)

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