On February 1, 2021 Sonnet BioTherapeutics Holdings, Inc., (NASDAQ:SONN) a clinical-stage company developing targeted immunotherapeutic drugs, reported that it has successfully completed a non-human primate (NHP) repeat-dose study of SON-1010, a proprietary fully human Interleukin 12 (IL-12) therapeutic candidate configured using Sonnet’s Fully Human Albumin Binding (FHAB) platform (Press release, Sonnet BioTherapeutics, FEB 1, 2021, View Source [SID1234576687]). The FHAB technology targets tumor tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of immunomodulatory cytokines.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The objectives of the study were to evaluate the toxicity of SON-1010 in a repeat dose regimen at two different doses and to gather critical data for the design of further IND-enabling safety and toxicity studies. The study included both intravenous and subcutaneous routes of administration with a total of two doses given 14 days apart. The high dosage rate utilized in this study was greater than 50 times the anticipated clinical level of exposure to patients.

Study results included:

Repeat dosing by intravenous and subcutaneous routes of administration were tolerated at both dose levels examined. As is typically observed with IL-12 administration, the white blood cell count dropped, and liver enzymes (ALT and AST) were elevated. These were transient effects that returned to baseline within 7 days following the second dose.
SON-1010-related changes in the physiological observations, body weight, pathology, cytokines and immunophenotyping were seen, all of which were consistent with those on-target effects previously observed in single dose studies.
A significant increase in Interferon-γ levels, a key pleiotropic cytokine associated with anti-tumor activity, was observed following the initial dose of SON-1010 with lower Interferon-γ levels observed following the second dose. This trend follows the published data from other studies of IL-12 in both humans and NHPs.
Pharmacokinetic analysis indicated a mean serum half-life of approximately 40 hours for animals administered SON-1010 via subcutaneous injection. This is consistent with data from the previously conducted dose escalation phase of the study, which demonstrates a substantial improvement in half-life compared to the 13-19-hour half-life of naked, recombinant human IL-12.
Pankaj Mohan, Ph.D., Sonnet founder and CEO, commented, "Taken in combination with our recent single dose toxicology results, these repeat dose data further reinforce our confidence in the SON-1010 safety and efficacy profile as we look forward to initiating the Phase 1 clinical development program later this year."

Sonnet used these data to inform the design of the ongoing GLP toxicity studies in preparation for IND submission. Additionally, the Company has developed a, continuous manufacturing platform consisting of an industry standard mammalian cell (Chinese Hamster Ovary or CHO) host cell line coupled with an intensified perfusion process that allows for rapid scale-up and commercial manufacturing, using state-of-the-art processes and technologies. The mammalian cell culture system enables glycosylation, thereby reducing the risk of immunogenicity.

Susan Dexter, Sonnet’s Chief Technology Officer added, "We have established an intensified, continuous manufacturing process, as compared with an industry standard fed batch process, to enhance productivity and improve the yield of difficult-to-express cytokines. We believe that the ability to manufacture SON-1010 as a single genetic sequence will enable scale up and optimize product quality. A lyophilization formulation provides stability and refrigerated cold chain simplicity."

On February 1, 2021 Revolution Medicines, Inc. (Nasdaq: RVMD) reported that it has commenced an underwritten public offering of 4,000,000 shares of common stock (Press release, Revolution Medicines, FEB 1, 2021, View Source [SID1234575012]). All of the shares of common stock are being offered by Revolution Medicines. In addition, Revolution Medicines intends to grant the underwriters a 30-day option to purchase up to an additional 600,000 shares of common stock.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

J.P. Morgan, Cowen, SVB Leerink and Guggenheim Securities are acting as the joint book-running managers for the proposed offering.

A registration statement relating to these securities has been filed with the Securities and Exchange Commission (SEC) but has not yet become effective. The offering is being made only by means of a prospectus, copies of which may be obtained, when available, from: J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department, by email at [email protected] or by telephone at (833) 297-2926; SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA, 02110, by telephone at 1-800-808-7525, ext. 6105, or by email at [email protected]; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On February 1, 2021 AIkido Pharma Inc. (Nasdaq: AIKI) ("AIkido" or the "Company") reported that the Company executed a Two Million Dollar Convertible Promissory Note Purchase Agreement with Convergent Therapeutics, Inc., securing an early investment in Convergen (Press release, Spherix, FEB 1, 2021, View Source [SID1234574715])t. Convergent has exclusive rights to technology related to next generation radiopharmaceutical therapy for prostate cancer that is covered by multiple issued U.S. and foreign patents.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Convergent is currently conducting advanced human trials relating to prostate cancer treatments involving peptide receptor radionuclide therapy ("PRRT") that targets the prostate-specific membrane antigen ("PSMA") present on prostate cancer cells. The technology was developed under the direction of Dr. Neil Bander, Professor of Urologic Oncology at Weill Cornell Medicine.

The key component of Convergent’s PRRT prostate cancer therapy is its proprietary drug, CONV 01-α, a monoclonal antibody conjugated with 225Ac, a radioactive alpha particle emitter. The function of CONV 01-α is unique in that it not only binds specifically to the PSMA receptor on prostate cancer cells, but also stimulates the internalization of the receptor along with itself and its powerful radioactive payload directly into tumor cells. Convergent is presently conducting two sets of human clinical trials using CONV 01-α as a single agent treatment for prostate cancer. The first is a Phase 1a/2a Single Ascending Dose Trial of CONV 01-α and the results are expected to be released in Q2 2021. In August of 2020, Convergent began a second Phase 1b/2a trial to test the efficacy of multiple ascending doses of CONV 01-α. If FDA approved, CONV 01-α would be the first antibody drug approved to direct a radioisotope into prostate cancer cells, and the first drug approved for the use of 225Ac in cancer treatment.

Leveraging the ability of CONV 01-α to internalize the PSMA receptor along with molecules bound to it, Convergent has also developed a proprietary dual therapy by adding a second molecule that specifically binds to PSMA and also contains a radioactive isotope. Convergent has identified certain small molecules that bind to PSMA, but at a different epitope than does CONV 01-α, and therefore do not interfere with the binding of CONV 01-α or its ability to internalize PSMA. The result is that two different radioactive drugs are internalized directly into prostate cancer cells. Importantly, Convergent identified small molecules, with a current focus on the molecule PSMA I&T, that have different biodistributions in the body than does CONV 01-α, so as to reduce additive damage from using two radioactive agents. PSMA I&T is a molecule routinely used clinically to perform imaging to show the presence and distribution of PSMA in a prostate cancer patient. Preliminary animal data using this proprietary dual action PRRT indicate that the two molecules administered together act in a truly synergistic fashion, i.e., the effect of using both drugs together is significantly higher than the expected additive effects of using each separately.

Convergent now has approval to begin human trials using CONV 01-α and PSMA I&T in a dual therapy, which are anticipated to begin in February of 2021. In these trials, Convergent will test PSMA I&T containing either 177Lu, a beta particle emitter, or 225Ac, the same alpha emitter in CONV 01-α. Convergent has approval to perform the three human trials listed below for this dual therapy, anticipated to begin in February of 2021:

(1) a Phase 1b/2a with the combination of CONV 01-α and PSMA I&T-β;

(2) a Phase 2b with the combination of PSMA I&T-β ± CONV 01-α, and

(3) a Phase 1b/2a with PSMA I&T-α ± CONV 01-α (i.e., both drugs with 225Ac, the α-particle emitter).

Another company is currently studying PSMA I&T-β, containing 177Lu, and has just completed a phase 3 trial in prostate cancer. Separately, Novartis is pursuing FDA approval for another 177Lu-small molecule drug for prostate cancer treatment, designated 177Lu-PSMA-617, which also binds PSMA. Novartis has recently completed a phase 3 registration trial for treatment of metastatic castration-resistant prostate cancer (mCRPC), a form of advanced prostate cancer. Like PSMA I&T-β, Novartis’s 177Lu-PSMA-617 may also be a promising candidate for use with CONV 01-α in the proprietary dual PRRT therapy.

Anthony Hayes, CEO of Aikido, stated, "This is by far the most advanced technology in which the Company has participated. The first of the human trials is wrapping up, with data to be reported shortly, and with the remaining trials either underway or scheduled to begin imminently. Participation in this advanced work represents a major and potentially transformative step for the Company and we are honored to be a part of it. I optimistically anticipate the first of the results to be released next quarter. We will update our shareholders as soon as the data is released."

On February 1, 2021 Bristol Myers Squibb’s Yervoy reported that it received approval for previously untreated non-small cell lung cancer in a combination of Opdivo and Yervoy (Press release, Bristol-Myers Squibb, FEB 1, 2021, View Source [SID1234574701]). Today, Merck released first-time data from the Phase III KEYNOTE-598 trial of Keytruda in combination with Yervoy (ipilimumab) compared to Keytruda alone as first-line therapy for metastatic non-small cell lung cancer (NSCLC) without EGFR or ALK genomic tumor aberrations and whose tumors express PD-L1. Adding Yervoy to the therapy did not improve overall survival (OS) or progression-free survival (PFS) but did add toxicity to Keytruda monotherapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In the study, median OS was 21.4 months in the Keytruda-Yervoy group compared to 21.9 months for the Keytruda only group. Also, the median PFS was 8.2 months in the combination cohort compared to 8.4 months for patients receiving Keytruda alone.

The trial enrolled 568 patients randomized 1:1 to receive Keytruda 200 mg intravenously on Day 1 of each three-week cycle for up to 35 cycles in combination with 1 mg/kg IV on Day 1 of each six-week cycle for up to 18 cycles of Yervoy, or Keytruda alone. There were no new safety signals for the Keytruda monotherapy arm, but in the combination arm, 76.2% reported treatment-related adverse events (TRAEs) compared to 68.3% of the Keytruda monotherapy arm. Of the TRAEs, 35.1% versus 19.6% were Grade 3-5, 27.7% versus 13.9% were serious, and 6.0% versus 3.2% led to discontinuation of Yervoy or placebo, and 19.1% versus 7.5% led to discontinuation of both drugs, while 2.5% versus 0.0% led to death.

There were also immune-mediated adverse events and infusion reactions in 44.7% of patients receiving the combination compared to 32.4% received Keytruda alone.

"In KEYNOTE-598, the addition of ipilimumab to Keytruda did not improve overall survival or progression-free survival, and patients who received the combination were more likely to experience serious side effects than those who received Keytruda monotherapy," said Michael Boyer, chief clinical officer and conjoint chair of thoracic oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia. "Keytruda monotherapy remains a standard of care for the first-line treatment of certain patients with metastatic non-small cell lung cancer whose tumors express PD-L1."

So basically, adding Yervoy to Keytruda failed to extend the lives of first-line NSCLC patients whose tumors expressed PD-L1 at a proportion of at least 50%, while increasing the serious side effects.

It has been hypothesized that by adding a CTLA-4-targeted antibody to a PD-1 checkpoint inhibitor would create more benefits in some cancers, but this is the first well-designed comparison trial. And it completely undercuts the hypothesis.

"The results are clear," said Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. "The combination did not add clinical benefit but did add toxicity."

The results were presented at the Presidential Symposium at the IASLC 2020 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer. The data was also published in the Journal of Clinical Oncology.

The trial was discontinued after a futility analysis by an independent Data Monitoring Committee (DMC), which declared the benefit/risk profile of the combination did not support continuing the trial.

Two primary forms of lung cancer are non-small cell and small cell. NSCLC is the most common type of lung cancer, making up about 85% of all lung cancer cases.

Sabine Maier, Bristol Myers Squibb’s head of oncology clinical development, noted that the benefit of the Opdivo-Yervoy combination "has been well established in Phase III trials across lung cancer, melanoma, renal cell carcinoma and mesothelioma" and those trials "clearly demonstrate that combining Yervoy and Opdivo can help patients achieve durable, long-term survival outcomes."

On February 1, 2021 argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases and cancer, reported that it has commenced a global offering of $750 million (approximately €618 million) of ordinary shares, which may be represented by American Depository Shares ("ADSs") (Press release, argenx, FEB 1, 2021, View Source [SID1234574666]). The global offering will be comprised of an offering of ordinary shares represented by ADSs in the United States and certain other countries outside of the European Economic Area and a simultaneous private placement of ordinary shares in the European Economic Area and the United Kingdom. Each of the ADSs represents the right to receive one ordinary share, nominal value of €0.10 per share. The U.S. offering and the European private placement are expected to close simultaneously.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In addition, argenx intends to grant the underwriters of the offering a 30-day option to purchase additional ordinary shares (which may be represented by ADSs) in an aggregate amount of up to 15% of the total number of ordinary shares (including represented by ADSs) proposed to be sold in the offering, on the same terms and conditions.

Baillie Gifford Overseas Limited and entities affiliated with it have indicated an interest in purchasing an aggregate of up to $415 million (approximately €342 million) of ordinary shares in this offering at the offering price per share and on the same terms as the other purchasers in this offering. However, because indications of interest are not binding agreements or commitments to purchase, the underwriters could determine to sell more, fewer or no ordinary shares to these potential purchasers, and these potential purchasers could determine to purchase more, fewer or no shares in this offering.

argenx’s ADSs are currently listed on the Nasdaq Global Select Market under the symbol "ARGX." and argenx’s ordinary shares are currently listed on Euronext Brussels under the symbol "ARGX.".

J.P. Morgan, Morgan Stanley, BofA Securities and Cowen are acting as joint bookrunning managers for the offering.

The securities are being offered in the United States pursuant to an automatically effective shelf registration statement that was previously filed with the Securities and Exchange Commission ("SEC"). A preliminary prospectus supplement relating to the securities being offered in the United States will be filed with the SEC and will be available on the SEC’s website at www.sec.gov.

When available, copies of the preliminary prospectus supplement and the accompanying prospectus relating to these securities being offered in the United States may be obtained for free from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; from Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, NY 10014, Attn: Prospectus Department, by email at [email protected], or by telephone at (866) 718-1649; from BofA Securities, NC1-004-03-43, 200 North College Street, 3rd floor, Charlotte, North Carolina 28255-0001, Attn: Prospectus Department, or by email at [email protected]; or from Cowen and Company, LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, Attn: Prospectus Department, by email at [email protected], or by telephone at (833) 297-2926.

A request for the admission to listing and trading of the ordinary shares (including the ordinary shares underlying the ADSs) on the regulated market of Euronext Brussels will be made following pricing of the offering.

This press release is for information purposes only and does not constitute, and should not be construed as, an offer to sell or the solicitation of an offer to buy or subscribe to any securities, nor shall there be any sale of securities in any jurisdiction in which such offer, solicitation or sale is not permitted or to any person or entity to whom it is unlawful to make such offer, solicitation or sale. Reference is also made to the restrictions set out in "Important information" below. This press release is not for publication or distribution, directly or indirectly, in or into any state or jurisdiction into which doing so would be unlawful or where a prior registration or approval is required for such purpose.