On January 31, 2022 Sierra Oncology, Inc. (Nasdaq: SRRA), a late-stage biopharmaceutical company dedicated to delivering targeted therapies for rare cancers, reported the closing of its previously announced underwritten public offering of 4,074,075 shares of its common stock at a price to the public of $27.00 per share and, in lieu of shares of common stock, to a certain investor, pre-funded warrants to purchase up to 925,925 shares of common stock at a price to the public of $26.999 per pre-funded warrant, which represents the per share public offering price for the common stock less the $0.001 per share exercise price for each pre-funded warrant (Press release, Sierra Oncology, JAN 31, 2022, View Source [SID1234607528]). The gross proceeds to Sierra Oncology from the offering were approximately $135.0 million, before deducting underwriting discounts and commissions and other offering expenses. Net proceeds to Sierra Oncology from the offering were approximately $126.6 million after deducting underwriting discounts and commissions and other offering expenses. Sierra Oncology intends to use the net proceeds of the offering to prepare for potential commercialization of momelotinib, clinical development of its other product candidates, research, clinical and process development and manufacturing of its product candidates, working capital, and capital expenditures and other general corporate purposes.

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!

Jefferies and Cantor are acting as the joint book-running managers and representatives of the underwriters for the offering. LifeSci Capital, Oppenheimer & Co. and H.C. Wainwright & Co. are acting as lead managers for the offering.

A shelf registration statement on Form S-3 relating to the securities offered in the public offering described above was filed with the Securities and Exchange Commission (SEC) on November 5, 2021 and declared effective by the SEC on November 12, 2021. A final prospectus supplement and accompanying prospectus relating to the offering have been filed with the SEC and are available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus may also be obtained by contacting Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388, or by email at [email protected]; or Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Avenue, New York, New York 10022, or by e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered 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 January 31, 2022 Tollys, a biopharmaceutical company developing the first anti-cancer immunotherapy based on a synthetic Toll-Like Receptor 3 (TLR3) specific agonist, reported that it has renewed and extended its research collaboration started in 2020 with a global pharmaceutical company, a leader in immuno-oncology (Press release, Tollys, JAN 31, 2022, View Source [SID1234607500]). The company also announces the acceleration and expansion of its R&D platform in the fields of TLR3 agonist candidates for intravenous administration and Antibody-Drug-Conjugates (ADC, or AOC for Antibody-Oligonucleotide-Conjugates).

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!

Based on the strong preclinical data collected to date with locally administered TL-532, Tollys is also accelerating and expanding its internal and collaborative R&D activities on TLR3 agonist candidates designed for intravenous administration and antibody-drug-conjugates. Tollys is thus running several parallel preclinical programs using different vectorization and targeting methods for its TLR3 agonist candidate(s). According to Tollys, TL-532 is the first chemically conjugable specific TLR3 agonist usable as a payload with antibodies and other carriers.

This acceleration in the development of candidates for intravenous administration is in line with the recommendations of the international board of the European oncology innovation acceleration program MATWIN which awarded Tollys TLR3 agonist the status of ‘best-in-class innovation of the year’ in May 2021.

"Our renewed and extended pharma collaboration is further confirmation of the potential of specific TLR3 agonists. We are also very excited to advance our R&D programs for the selection of candidates for intravenous administration; we estimate that a lot more patients could benefit from treatment with TLR3 agonists, if administered intravenously rather than locally," said Vincent Charlon, CEO of Tollys.

About TL-532
TL-532 is the first synthetic specific TLR3 agonist with a proprietary defined double-stranded RNA sequence. As such, TL-532 has the potential to be the best-in-class and first-to-market TLR3 agonist. TL-532 was shown to have a triple mechanism of action inducing 1) death by apoptosis selective to cancer cells-not in normal cells, leading to the in-situ release of tumor specific antigens, 2) activation of the myeloid dendritic cells of the immune system to mount a specific T-cell response against the tumor antigens and 3) switch of the tumor microenvironment, by producing cytokines and chemokines which prevent tumor development. The result is the immunogenic cell death of tumor cells, together with an autovaccination preventing the recurrence of cancer.

On January 31, 2022 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage cancer immunotherapy company developing novel biotherapeutics targeting immunosuppressive myeloid checkpoints, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for IO-202, a first-in-class antibody targeting leukocyte immunoglobulin-like receptor B4 (LILRB4, also known as ILT3), for the treatment of solid tumors (Press release, Immune-Onc Therapeutics, JAN 31, 2022, View Source [SID1234607529]).

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!

Myeloid cells are abundant and often immune suppressive in the solid tumor microenvironment. The LILRB4 receptor is expressed on monocytic myeloid cells, including dendritic cells, and contributes to a tolerogenic myeloid cell phenotype, resulting in decreased tumor immune surveillance. In preclinical data presented at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, IO-202 was found to enhance dendritic cell function and T cell activation in vitro and promote anti-tumor immunity in a solid tumor model in vivo. These data provided a strong rationale to evaluate the therapeutic potential of IO-202 as a myeloid checkpoint inhibitor in solid tumors.

"The FDA clearance to begin our Phase 1 study for IO-202 in solid tumors is a major milestone for Immune-Onc, which represents the third IND for our pipeline and the second for IO-202," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "We know that high LILRB4 expression on myeloid cells infiltrating solid tumors contributes to tumor immune evasion. IO-202 is a first-in-class myeloid checkpoint inhibitor targeting LILRB4, which may provide therapeutic benefit to multiple solid tumor types where evasion of the immune system allows disease to progress and create resistance to therapy, including to T cell checkpoint inhibitors. We look forward to advancing IO-202 into the clinic to evaluate its potential as a monotherapy and in combination with an anti-PD-1 in patients with solid tumors."

The Phase 1, multicenter, dose-escalation and dose expansion study will consist of a monotherapy cohort and a combination therapy cohort to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of IO-202 alone and in combination with pembrolizumab, an anti-PD-1 antibody, followed by indication-specific expansion cohorts to be treated with IO-202 in combination with pembrolizumab at the recommended Phase 2 dose. Various biomarkers will be assessed to enable a mechanistic understanding of clinical data and inform future trials. This study may also provide an opportunity to identify preliminary efficacy signals.

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune inhibitory transmembrane protein found on monocytic myeloid cells, including dendritic cells. LILRB4 inhibits antigen-presenting cell activation, resulting in immune tolerance. LILRB4 is also expressed on certain hematologic cancer cells and monocytic myeloid cells in the solid tumor microenvironment. Immune-Onc and The University of Texas published pioneering research in Nature illuminating the role of LILRB4 in immune suppression and tumor infiltration in acute myeloid leukemia (AML) and presented the rationale for targeting LILRB4 in solid tumors at the AACR (Free AACR Whitepaper) Annual Meeting 2021.

ABOUT IO-202

IO-202 is a first-in-class LILRB4 antagonist antibody with broad potential as an immunotherapy in both blood cancers and solid tumors. In hematologic malignancies, preclinical studies showed that IO-202 converts a "don’t kill me" to a "kill me" signal by activating T cell killing and converts a "don’t find me" to a "find me" signal by inhibiting infiltration of blood cancer cells. In solid tumors, preclinical data showed that IO-202 enhances dendritic cell function and T cell activation in vitro and inhibits tumor growth in a solid tumor model in vivo.

IO-202 is currently in Phase 1 clinical development for the treatment of AML and chronic myelomonocytic leukemia (CMML). The U.S. Food and Drug Administration granted IO-202 Orphan Drug Designations for treatment of AML in 2020. The company has received IND clearance to evaluate IO-202 in solid tumors in January 2022.

On January 30, 2022 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that LENVIMA (generic name: lenvatinib mesylate), the multiple receptor tyrosine kinase inhibitor discovered by Eisai, in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.’s KEYTRUDA (generic name: pembrolizumab) has been approved in Taiwan for the first-line treatment of patients with advanced renal cell carcinoma (RCC) (Press release, Eisai, JAN 30, 2022, View Source [SID1234607492]). This marks the first approval for LENVIMA which will be used in combination with KEYTRUDA for advanced RCC in Asia.

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 approval is based on results from the CLEAR (Study 307)/KEYNOTE-581 trial evaluating the combination for the first-line treatment of patients with advanced RCC. These results were presented at the 2021 Genitourinary Cancers Symposium (ASCO GU) and simultaneously published in the New England Journal of Medicine. 1 In this trial, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements in the primary efficacy outcome measure of progression-free survival (PFS), as well as the key secondary efficacy outcome measures of overall survival (OS) and objective response rate (ORR) versus sunitinib. For PFS, LENVIMA plus KEYTRUDA reduced the risk of disease progression or death by 61% (HR=0.39 [95% CI: 0.32-0.49]; p<0.0001) with a median PFS of 23.9 months versus 9.2 months for sunitinib. For OS, LENVIMA plus KEYTRUDA reduced the risk of death by 34% (HR=0.66 [95% CI: 0.49-0.88]; p=0.0049) versus sunitinib. Additionally, the confirmed ORR was 71% (95% CI: 66-76) (n=252) for patients who received LENVIMA plus KEYTRUDA versus 36% with sunitinib (95% CI: 31-41) (n=129). LENVIMA plus KEYTRUDA achieved a complete response (CR) rate of 16% and partial response (PR) rate of 55% versus a CR rate of 4% and a PR rate of 32% for those who received sunitinib. 2 In this trial, the five most common adverse reactions (any grade) observed in the LENVIMA plus KEYTRUDA combination arm were fatigue, diarrhea, musculoskeletal disorders, hypothyroidism and hypertension. 2

Worldwide, it is estimated there were more than 430,000 new cases of kidney cancer diagnosed and more than 180,000 deaths from the disease in 2020. 3 In Taiwan, there were more than 1,400 new cases and more than 600 deaths in 2018. 4 Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCC. 5 Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. 6 Approximately 30% of patients with RCC will have metastatic disease at diagnosis, and as many as 40% will develop metastases after primary surgical treatment for localized RCC. 7,8　 The prognosis for these patients is poor as survival is highly dependent on the stage at diagnosis, and the five-year survival rate is 12% for patients diagnosed with metastatic disease. 8

Eisai positions oncology as a key therapeutic area and is aiming to discover innovative new medicines with the potential to cure cancer. Eisai is committed to expanding the potential clinical benefits of lenvatinib for cancer treatment, as it seeks to contribute to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families and healthcare professionals.

*In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with the anti-PD-1 therapy pembrolizumab from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

On January 30, 2022 Akeso, Inc. (9926.HK) reported that the Ligufalimab (CD47 monoclonal antibody, research and development code: AK117, the novel immuno-oncology drug independently developed by the Company) and Ivonescimab (PD-1/VEGF bi-specific antibody, research and development code: AK112) has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People’s Republic of China (”China”) to initiate a phase II clinical trial with chemotherapy as first-line therapy for unresectable locally advanced or metastatic triplenegative breast cancer (Press release, Akeso Biopharma, JAN 30, 2022, View Source [SID1234607495]).

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!

This clinical trial is an open and multi-center phase II clinical trial, which plans to include patients who have not received systemic anti-tumor therapy, are not suitable for radical surgical resection or local therapy, or subjects with locally advanced or metastatic triple-negative breast cancer whose disease progresses after surgical resection or local therapy.

Breast cancer is the most prevalent malignant tumor in women worldwide and in China, among which triple-negative breast cancer (that is, negative for progesterone receptor, estrogen receptor and human epidermal growth factor receptor 2) is highly aggressive and has a high recurrence rate, with a relatively poor prognosis. It is the subtype with the highest recurrence rate and mortality in breast cancer, accounting for approximately 15% of all breast cancers.

Related studies have shown that the mechanisms by which tumor cells evade the innate and adaptive immune systems play a key role in the occurrence and development of recurrent and/or metastatic tumors. An important mechanism of immune escape in triple-negative breast cancer is the expression of CD47. CD47 inhibits the phagocytosis of macrophages by releasing a ”don’t eat me” signal, and at the same time suppresses adaptive immunity by interacting with dendritic cells.

Under the tumor microenvironment, there is a strong correlation between VEGF and PD-1 expression. Therefore, the use of a bi-specific antibody to block PD-1 and VEGF simultaneously can provide a type of drug with more targets in the tumor microenvironment.

Related studies have also shown that the up-regulation of CD47 can inhibit the phagocytosis of macrophages and the anti-tumor effect of VEGF/VEGFR inhibitors. It can also induce the up-regulation of CD47 during anti-angiogenesis therapy. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway induced by antiangiogenesis therapy (up-regulation of CD47) while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.

Therefore, the combination therapy of Ivonescimab and Ligufalimab is expected to activate both innate and adaptive immune pathways and enhance the targeted recognition of tumors by the immune system, which can create a synergy effect of immunity, anti-angiogenesis and chemotherapy. It is expected to achieve better anti-tumor effects in subjects with advanced triple-negative breast cancer.