WHAT is the $5 Billion for? Part of the partnering dance? Defence against hostile takeover threat? Here is the summary of what Sorrento is doing...
"At our core, we are antibody-centric and leverage our proprietary G-MAB™ library and targeted delivery modalities to generate the next
generation of cancer therapeutics. Our fully human antibodies include PD-1, PD-L1, CD38, CD123, CD47, BCMA, LAG3, CTLA-4, CD137 and SARSCoV-2 neutralizing antibodies, among others. We also have programs assessing the use of our technologies and products in pain, autoimmune,
inflammatory, viral and neurodegenerative diseases.
Our vision is to leverage these antibodies in conjunction with proprietary targeted delivery modalities to generate the next generation of cancer
therapeutics. These modalities include proprietary chimeric antigen receptor T-cell therapy, or CAR-T, dimeric antigen receptor T-cell therapy, or DART™, antibody drug conjugates, or ADCs, as well as bispecific antibody approaches. We acquired SOFUSA
®, a drug delivery technology, in July 2018,
which delivers biologics or other drugs directly into the lymphatic system to potentially achieve improved efficacy and reduce adverse effects compared to
standard parenteral therapy. Additionally, our majority-owned subsidiary, Scilex Holding Company, or Scilex Holding, acquired the assets of Semnur
Pharmaceuticals, Inc., or Semnur, in March 2019. Semnur’s SEMDEXA
TM, or SP-102, compound has the potential to become the first U.S. Food and Drug
Administration, or FDA,-approved epidural steroid product for the treatment of sciatica. In response to the global SARS-CoV-2, or COVID-19, pandemic,
we are utilizing the Bruton’s tyrosine kinase, or BTK, inhibitor (Abivertinib, acquired from ACEA Therapeutics, Inc.) to treat the cytokine storm associated
with a COVID-19 infection. We are also internally developing and conducting clinical studies for potential coronavirus antiviral therapies and vaccines,
including COVI-MSC™, COVI-AMG™, COVIDROPS™, and COVISHIELD™; and diagnostic test solutions, such as COVISTIX™.
With each of our clinical and preclinical programs, we aim to tailor our therapies to treat specific stages in the evolution of a disease, from
elimination to equilibrium and escape. In addition, our objective in our immuno-oncology programs is to focus on tumors that are resistant to current
treatments and where we can design focused trials based on a genetic signature or biomarker to ensure patients have the best chance of a durable and
significant response. We have several immuno-oncology programs that are in or near to entering the clinic. These include cellular therapies, oncolytic
viruses (SeprehvecTM) and a palliative care program targeted to treat intractable pain in advanced cancer and osteoarthritis (resiniferatoxin, or RTX). Our
cellular therapy programs focus on our allogeneic DAR-T platform for adoptive cellular immunotherapy to treat both solid and liquid tumors.
From the start of the COVID-19 pandemic, our mission has been in part to leverage our deep expertise in developing targeted antibodies for
cancer immunotherapy to create best-in-category treatments and diagnostics to ease suffering and assist in the global response to COVID-19. We have
leveraged, and continue to leverage, our G-MAB library and antibody development engineering capabilities to advance promising diagnostics and
neutralizing antibody candidates to test and treat COVID-19 and the immune reactions associated with SARS-CoV-2 infection.
STI-2020, or plutavimab, is a highly potent neutralizing antibody, or nAb, directed against SARS-CoV-2 that is currently being developed as an
intranasal instillation as STI-2099, or COVI-DROPS. STI-2020, the intravenous, or IV, formulation and COVI-DROPS were both cleared by the FDA for
Phase I healthy volunteer studies, which were completed and demonstrated that the nAbs were well-tolerated (IV up to 200 mg and intranasal up to 60 mg)
without dose limiting toxicity or severe or serious adverse events. Most adverse events were mild and not treatment related. Phase II studies of COVIDROPS in outpatients with COVID-19 have begun enrollment in the U.S. and the United Kingdom and enrollment in Mexico is expected to commence in
Q1 2022. The UK study is expected to reach the planned interim analysis threshold in late January 2022. The study in Mexico is anticipated to begin
pediatric enrollment in early 2022. We are also developing a cocktail of STI-2020 and STI-9167 (a second, independently developed nAb) (COVISHIELD™) to be formulated both for IV and intranasal administration, which in preclinical studies has been broadly effective against emerging variants of
concern. A healthy subject study for STI-9167 (IV formulation) and STI-9199 (intranasal formulation) is expected to begin in early Q1 2022 with Phase II
studies of COVI-SHIELD to follow.
We have also developed two promising potential rescue treatments with Abivertinib (STI-5656), an oral next generation dual EGFR, or epidermal
growth factor receptor, mutants/BTK inhibitor, to treat hospitalized COVID-19 patients and COVI-MSC (samtonadstrocel or STI-8282), human allogeneic
adipose-derived mesenchymal stromal cells, for patients suffering from COVID-19-induced acute respiratory distress. Both have been cleared by the FDA
for Phase II studies and we have completed Phase II clinical studies in the U.S. and Brazil of Abivertinib to treat COVID-19-induced acute respiratory
distress syndrome, or ARDS. While all patient groups improved with treatment, the U.S. study identified an at-risk population who were the best
responders: those who required oxygen supplementation with non-invasive ventilation or high flow oxygen at baseline. While the Brazil study did not
enroll a population as sick as those in the U.S. study, the results were similarly supportive. In the U.S. study, the at-risk patients treated with Abivertinib
were discharged from the ICU on average two days sooner than those patients that received the standard of care and placebo. In both the Brazil and U.S.
studies, there was nearly a 50% reduction of death and/or mechanical ventilation or extracorporeal membrane oxygenation in the Abivertinib treated patient
group by day 29 as compared to the placebo group. These data were used to power a pivotal Phase III Abivertinib study, which is expected to begin
enrollment in Q2 2022. Two separate COVI-MSC studies are currently enrolling in Brazil (pivotal trial) and in the U.S. (Phase II) for patients with
COVID-19-induced ARDS. We are also working with Brazilian regulators (ANVISA) to conduct a COVID-19 study with COVI-MSC in pulmonary longhaul patients post recovery from the acute infection.
In furtherance of our goal to develop products across the entire continuum of COVID-19 solutions, we are further developing highly sensitive and
rapid diagnostic tests. COVISTIX™ is a lateral flow antigen test that uses a proprietary platinum-based colloid and antibody combination, resulting in high
sensitivity and accuracy. This is a simple and rapid (15-minute) test with a nasal swab and is designed for point-of-care and at-home use. This product has
been approved for use in Mexico and Brazil as a point-of-care test and also has received its CE mark.
We previously reported early data from Phase I trials of our carcinoembryonic antigen, or CEA,-directed CAR-T program. We treated five patients
with stage 4, unresectable adenocarcinoma (four with pancreatic and one with colorectal cancer) and CEA-positive liver metastases with anti-CEA CAR-T.
During 2021, we decided to pivot away from an autologous CAR-T platform to allogeneic DAR-T (dimeric antigen receptor T cell) and successfully
submitted an Investigational New Drug application, or IND, for our CD38 DAR-T candidate for relapsed or refractory multiple myeloma, or RRMM, and
obtained FDA clearance in August 2021. We anticipate the first patient to be enrolled in early Q1 2022.
We also successfully submitted INDs for our anti-CD47 mAb (STI-6643), TROP2 ADC, or STI-3286, and Seprehvec™, or STI-1386, our secondgeneration oncolytic virus. We dosed the first patient in a Phase 1b study with STI-6643 and are awaiting follow-up data. A parallel study is also planned
for STI-6643 in China. We anticipate the first patient to be enrolled in the U.S. study with our anti-TROP2 ADC in Q1 2022. This ADC has a drug payload
SN38 (a DNA polymerase inhibitor) targeting various solid tumors. Unlike other anti-TROP2 ADC products on the market, ours has a stable covalent
linker that is designed to prevent premature release of the toxin to avoid its toxicity. Our TROP-2 ADC also has been approved for clinical trials in China
by our partner and is expected to soon enroll the third cohort. Finally, we anticipate the first patient to be enrolled in the Seprehvec study in Q1 2022.
Additionally, based upon our exclusive licensing arrangement with Mayo Clinic for its antibody-drug-nanoparticle albumin-bound (ADNAB™)
platform, the next generation in ADC technology, we intend to file several INDs to treat various cancer targets. With respect to Abivertinib, our oral small
molecule combined EGFR mutants/BTK inhibitor, we are waiting for a final imaging read of Phase III data with additional follow-up from patients who
continued on treatment in the years since the last update presented at the 2019 American Society of Clinical Oncology annual meeting. We anticipate
requesting a pre-new drug application, or NDA, meeting with the FDA to discuss the pathway to a planned NDA filing. Finally, we intend to start studies in
castrate resistant prostate cancer with Abivertinib in the U.S. in Q1 2022 and in Brazil in Q2 2022.
With respect to our anti-CD38 ADC program, we began enrolling patients in the first quarter of 2021 in a Phase Ib ascending dose study for
systemic Amyloid light-chain amyloidosis. We intend to start a new study to target RRMM in Q1 2022 and are planning to target metastatic esophageal and
lung cancer to treat T-cell acute lymphoblastic leukemia. We also have an ongoing partnership with Mayo Clinic to explore the use of lymphatic delivery
using our SOFUSA microneedle array device. Lymphatic delivery of products traditionally delivered by IV administration has the potential to improve the
pharmacokinetic profile and efficacy while reducing their adverse events profile. We also have an active program using the SOFUSA delivery system to
treat rheumatoid arthritis patients resistant to etanercept and expect to announce preliminary results from an ongoing Phase I study in Q1 2022.
Broadly speaking, we believe we are one of the world’s leading cellular therapy companies today due to our investments in technology and
infrastructure, which have enabled significant progress in developing our next-generation non-viral, “off-the-shelf” allogeneic DAR-T solutions. With such
solutions, DAR-T therapy can become a versatile drug product platform capable of delivering multiple targeted therapeutic approaches.
Outside of immuno-oncology programs, as part of our global aim to provide a wide range of therapeutic products to meet underserved markets, we
have made investments in non-opioid pain management. These include RTX, a non-opioid naturally-occurring chemical that specifically targets transient
receptor potential vanilloid-1, or TRPV1. Depending on the site of injection, RTX can ablate or destroy targeted nerves (e.g., an epidural injection) or
temporarily defunctionalize them (peripheral injections such as intra-articular). TRPV1 largely is responsible for the noxious chronic and inflammatory
pain signaling that can occur post trauma but leaves other nerve functions intact. RTX has been granted orphan drug status for the treatment of intractable
pain with end-stage or advanced cancer and two Phase Ib first-in-human trials (intrathecal and epidural routes) were completed. A Phase Ib trial studying
the safety and efficacy of RTX to treat moderate to severe osteoarthritis, or OA, knee pain was completed in early 2021 with one year follow-up data and
preliminary results showing the potential for long-term efficacy with no dose limiting toxicity. We have received clearance to proceed with Phase II clinical
trials of RTX to treat severe cancer pain (epidural) and moderate-to-severe OA of the knee pain (intra-articular). The knee OA study began enrolling in Q4
2021 and the epidural cancer pain study is expected to start enrolling in Q1 2022.
Also, in this area, we have developed in-house and acquired proprietary technologies to responsibly develop next generation, branded
pharmaceutical products to better manage patients’ medical conditions, maximize the quality of life of patients and assist healthcare providers. The flagship
product of Scilex Holding, ZTlido® (lidocaine topical system 1.8%), is a next-generation lidocaine delivery system, which was approved by the FDA for
the treatment of postherpetic neuralgia, a severe neuropathic pain condition in February 2018, and was commercially launched in October 2018. Scilex
Holding has built a full commercial organization, which includes sales, marketing, market access and medical affairs.
Recent Developments
On December 9, 2021, Scilex Holding announced highly statistically significant positive top-line results from its Phase III SP-102 (SEMDEXA™)
Pivotal Trial C.L.E.A.R Program for its novel, non-opioid, corticosteroid formulation, injectable dexamethasone sodium phosphate viscous gel product for
the treatment of lumbosacral radicular pain (sciatica). SEMDEXA has received Fast Track status from the FDA.
The C.L.E.A.R. Program trial met the primary efficacy and key secondary efficacy endpoints:
· For the primary endpoint of change in average daily pain (as measured by the Numeric Pain Rating Scale) in the affected leg over 4 weeks
following the initial injection the LS Mean (SE) group difference of -1.08 (0.17) compared to placebo with a p-value <0.001.
· The two key secondary endpoints assessing Oswestry Disability Index (ODI) and Time to open-label repeat injection have also demonstrated
highly statistically significant results for SP-102. The LS Mean (SE) group difference in ODI compared to placebo at week 4 was -6.28 (1.49) with
a p-value <0.001. A Cox proportional hazard model showed significantly longer duration of initial SP-102 (SEMDEXA™) treatment compared to
placebo Hazard Ratio (95% CI) 0.49 (0.36, 0.65), with a p-value <0.001.
For a complete description of our business, financial condition, results of operations and other important information, we refer you to our filings..."
