On December 13, 2021 Bionomics Limited (Bionomics or Company), a clinical-stage biopharmaceutical company, reported the launch of its initial public offering (the Offering) of 1,620,000 American Depositary Shares (ADSs), each representing 180 ordinary shares, in the United States (Press release, Bionomics, DEC 13, 2021, View Source [SID1234596999]). The target size of the of the Offering is US$25.0 million in gross proceeds.

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All ADSs to be sold in the Offering will be sold by Bionomics. In addition, Bionomics expects to grant the underwriters an option to purchase up to an additional 243,000 ADSs within 30 days from the date of the final prospectus at the initial public offering price, less underwriting discounts and commissions.

Bionomics has applied to have its ADSs listed on the Nasdaq Global Market under the symbol "BNOX." Bionomics’ ordinary shares are currently traded on the Australian Securities Exchange (ASX) under the symbol "BNO."

Evercore ISI and William Blair are acting as lead book-running managers for the Offering. Cantor, Berenberg and H.C. Wainwright & Co. are acting as book-running managers for the Offering.

The Offering will be made only by means of a prospectus under the U.S. Securities Act of 1933. When available, copies of the preliminary prospectus relating to and describing the terms of the Offering may be obtained from (i) Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 35th Floor, New York, New York 10055, or by telephone at (888) 474-0200, or by email at [email protected] ; or (ii) William Blair & Company, L.L.C., Attention: Prospectus Department, 150 North Riverside Plaza, Chicago, Illinois 60606, or by telephone at (800) 621-0687, or by email at [email protected] . Australian investors are only eligible to invest under the prospectus if they are exempt from disclosure as sophisticated or professional investors under the Corporations Act 2001 (Cth).

A registration statement relating to these securities has been filed with the U.S. Securities and Exchange Commission but has not yet become effective. These securities may not be sold, nor may offers to buy these securities be accepted, prior to the time the registration statement becomes effective. This press release shall not constitute an offer to sell or a solicitation of an offer to buy the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. As disclosed in the registration statement, the underwriters may purchase and sell ADSs in the open market, including to cover over-allotments.

Released on authority of the Company Secretary.

On December 13, 2021 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a biopharmaceutical company committed to transforming the discovery and development of novel antibody-based immunotherapies, reported preclinical data demonstrating the compelling differentiation of ADG153, an anti-CD47 monoclonal antibody (mAb), and ADG152, a CD20xCD3 bispecific T-cell engager (TCE) (Press release, Adagene, DEC 13, 2021, View Source [SID1234597081]). The data were presented in two poster presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition taking place December 11-14, 2021, which are available in the Publications section of the company’s website at www.adagene.com.

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"Our novel anti-CD47 antibody and CD20xCD3 bispecific TCE programs successfully leverage SAFEbody technology for precision masking to decouple efficacy from the toxicities that are often associated with therapeutic modalities for these two important targets on the forefront of clinical development for hematologic malignancies," said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. "Our preclinical evaluation shows the desirable target product profiles of these two transformative programs emerging from our deep, broad and differentiated pipeline. In particular, we are very excited about our highly differentiated anti-CD47 SAFEbody in IgG1 format, which introduces IgG1-mediated effects for potent tumor killing with a compelling safety profile and 8-fold prolonged half-life. Our first POWERbody CD20xCD3 bispecific TCE with precision masking on our tailor-made anti-CD3 arm is highly differentiated, engineered for potent and sustained tumor killing with more than 100-fold cytokine release control and 2-3-fold prolonged half-life in comparison with a benchmarked antibody in clinical development. Together, these two programs highlight the strength of our AI-powered antibody platform, paving the way for explosive growth of our pipeline."

ADG153 (Anti-CD47 SAFEbody)

Key findings from the poster (#3342) titled "ADG153, an Anti-CD-47 Monoclonal Antibody Prodrug, Has Strong In Vivo Anti-Tumor Activity, Minimal RBC-Related and Antigen Sink Liabilities, and Extended Half Life in Comparison with Benchmark Clinical Antibodies of the Same IgG Subclass" include:

Given the dose-limiting hematologic toxicity and antigen sink liability associated with current anti-CD47 antibodies in clinical development, Adagene has developed an anti-CD47 SAFEbody with precision masking for preferential binding on CD47 overexpressed on tumor versus normal cells. To realize the full potential of anti-CD47 therapy for both hematologic and solid malignancies, the SAFEbody technology enables IgG1-mediated strong effector functions for potent tumor killing, while minimizing antigen sink and red blood cell (RBC) depletion with an approximately 8-fold prolonged half-life for convenient drug dosing and administration.
An anti-CD47 ADG153-G4 SAFEbody was designed for benchmarking and evaluated in preclinical studies in comparison with its parental antibody, and analogs of magrolimab (Hu5F9) and lemzoparlimab (TJC4) in IgG4 format with the following findings:

ADG153-G4 parental antibody and its activated SAFEbody can block the CD47 signal by targeting a unique epitope of CD47 with high affinity and minimal RBC hemagglutination.
In preclinical studies in monkeys, ADG153-G4 showed a significantly less decrease in RBCs and hemoglobin at the 10, 30 and 60 mg/kg dose levels compared to Hu5F9 at 10 mg/kg, addressing the hematologic toxicities inherent in current anti-CD47 therapies in development.
ADG153-G4 SAFEbody also showed its 8-fold prolonged half-life by overcoming the antigen sink observed with other anti-CD47 therapies in development.
Only antibody-dependent cellular phagocytosis (ADCP) effector function was detected for anti-CD47 antibodies in IgG4 isotype via CD47-mediated phagocytosis by macrophage.
An anti-CD47 ADG153-G1 SAFEbody was designed to maximize tumor killing via IgG1-mediated effector functions unlike many other anti-CD47 therapies in development:

ADG153-G1 induced potent antibody-dependent cellular cytotoxicity (ADCC); as expected, none was observed for the IgG4 benchmark antibodies.
ADG153-G1 induced stronger ADCP activity than the IgG4 benchmark antibodies.
Preclinical results concluded that the ADG153-G1 can achieve potent anti-CD47 efficacy with a well-tolerated safety profile, providing a strong rationale to advance this candidate into clinic. Currently, no other known anti-CD47 antibodies using the IgG1 isotype are in clinical development.

Notably, ADG153-G1 was well tolerated at 10 mg/kg, with only an 8 percent decrease in RBCs, compared to a 49 percent decrease with Hu5F9 in IgG4 format. For reference, it has been reported in the literature that another IgG1 anti-CD47 antibody can cause more than a 40 percent decrease in RBCs at 1 mg/kg.
After a single intravenous dose, ADG153-G1 demonstrated an approximately 8-fold longer apparent half-life and 5-fold higher area under the curve (AUC) at 10mg/kg than Hu5F9.
Taken together, these preclinical findings suggest that the ADG153-G1 SAFEbody integrates safety (by precision masking) and efficacy (by IgG1-mediated ADCC and ADCP) into one single modality for a best-in-class product profile, presenting the exciting opportunity to maximize potential of anti-CD47 therapy – ultimately aimed for solid malignancies.
ADG152 (CD20xCD3 POWERbody)

Key findings from the poster (#1204) titled "ADG152, a Novel CD20xCD3 T-Cell Engager Prodrug with Enhanced Therapeutic Index, Demonstrates Strong Anti-Tumor Activity with Improved Safety" include:

ADG152 is a bispecific CD20xCD3 T-cell engager POWERbody that integrates SAFEbody precision masking technology to minimize cytokine release syndrome (CRS) and on-target/off-tumor toxicities for an increased therapeutic index.
The anti-CD20 arm of ADG152 has enhanced the binding to CD20, while its anti-CD3 arm has tailor made affinity for CD3 using SAFEbody technology.
At a 100-fold higher dose, ADG152 at 30 mg/kg resulted in significantly less cytokine induction (as measured by IFN-γ and IL-2 levels) than an analog of plamotamab at 0.3 mg/kg.

In preclinical models, ADG152 resulted in dose-dependent anti-tumor activity with almost complete tumor growth inhibition when dosed at 1.5 mg/kg.

ADG152 induced strong and sustained B-cell depletion across different dose levels.

ADG152 also demonstrated improved pharmacokinetics in monkeys versus the plamotamab analog, with approximately a 2-fold longer half-life (7-13 days at 0.3 – 30mg/kg) and approximately an 8-fold higher AUC after a single intravenous injection.
"CRS has been a longstanding challenge of T-cell engagers and has limited the ability to safely provide high levels of activity during initial dosing," said Stanley Frankel, M.D., a clinical advisor who contributed to development and approval of blinatumomab (Blincyto) while working at Micromet and Amgen. "I am encouraged that the preclinical profile of ADG152 offers potential to provide a way to simplify treatment by avoiding step dosing and pretreatment with steroids, while also enhancing efficacy of this POWERbody to engage T-cells to attack tumor targets."

Both ADG153 and ADG152 are potential Investigational New Drug candidates from Adagene’s growing portfolio of preclinical discovery programs, five of which are in IND-enabling studies. The preclinical data presented at ASH (Free ASH Whitepaper) provide a strong rationale for advancing these potentially best-in-class candidates into clinical development.

On December 13, 2021 BerGenBio ASA (OSE:BGBIO), BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that it is presenting updated data from the Company’s Phase II study of bemcentinib (BCBC003) in a poster presentation today at the 63rd Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting (Press release, BerGenBio, DEC 13, 2021, View Source [SID1234596911]).

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Professor Sonja Loges will provide an update from the Company’s Phase II study (BGBC003) of bemcentinib in combination with low dose cytarabine (LDAC) in older, relapsed and refractory AML patients unfit for intensive chemotherapy.

The data presented indicate that bemcentinib in combination with LDAC is well tolerated and offers meaningful clinical benefits. Translational research has identified immune-based activity associated with response to treatment, demonstrating that bemcentinib elicits activation of CD8+ T cells and B cells/plasma cells, two major adaptive immune cell populations responsible for anti-AML immune responses. Survival data measured as median Overall Survival (mOS) in older unfit relapsed AML patients looks encouraging compared to historical controls all through not yet matured.

Professor Sonja Loges, Chief Investigator of the BGBC003 trial commented: "The data on relapsed AML patients who currently have very few treatment options, is very encouraging. These results affirm our belief that the combination of bemcentinib and LDAC provides meaningful clinical benefits."

Details of the presentation:

Title: Bemcentinib (Oral AXL Inhibitor) in combination with Low-dose Cytarabine Is Well Tolerated and Efficacious in Older Relapsed AML Patients. Updates from the Ongoing Phase II Trial (NCT02488408) and Preliminary Translational Results indicating Bemcentinib elicits anti-AML immune responses.

Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III

Time, Location: 6.00 – 8.00 PM Eastern, Georgia World Congress Center, Hall B5

On December 13, 2021 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported final results from a Phase 2 study of tipifarnib as a monotherapy in patients with relapsed or refractory T-cell lymphoma, including an overall response rate (ORR) of 56% and a median overall survival of 32.8 months in heavily pretreated patients with angioimmunoblastic T-cell lymphoma (AITL) (Press release, Kura Oncology, DEC 13, 2021, View Source [SID1234596928]).

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The final results are being presented during an oral session today at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual meeting in Atlanta. A copy of the presentation is available on the Company’s website at www.kuraoncology.com.

"These data compare favorably to approved therapies for treatment of relapsed/refractory T-cell lymphoma, particularly in patients with AITL for whom there are few treatment options," said Thomas Witzig, M.D., a Hematologist at Mayo Clinic and the study’s lead investigator.

​A total of 65 patients with relapsed or refractory T-cell lymphoma were enrolled in the study, with a median of three prior regimens (range 1-8). Twenty-five patients (38%) received prior autologous stem cell transplant. The ORR among all efficacy-evaluable patients was 40% (23/58) and the median duration of response (DOR) was 4.6 months.

Notably, the ORR in patients with AITL, an aggressive form of T-cell lymphoma and a pre-specified subgroup in the trial, was 56% (18/32), including nine complete responses, with a median DOR of 7.8 months and a median overall survival of 32.8 months.

Tipifarnib was generally well-tolerated in this Phase 2 study, with adverse events consistent with its known safety profile. The most frequently observed treatment-related adverse events (all grades) were hematological (neutropenia, thrombocytopenia, anemia) and gastrointestinal (nausea, diarrhea), as well as fatigue.

"We continue to be encouraged by the growing body of data for tipifarnib in both solid tumors and hematologic malignancies," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "The clinical benefit demonstrated in late-stage patients with T-cell lymphoma, including heavily pretreated patients with AITL, underscore the potential of farnesyl transferase inhibition to drive clinical benefit in patients with cancer."

This multi-center, single-arm, open-label Phase 2 study was designed to evaluate tipifarnib as a monotherapy in adult patients with relapsed or refractory T-cell lymphoma. The primary objective of the study was to determine the antitumor activity by ORR. Secondary objectives included safety, DOR and progression-free survival, and exploratory analyses included overall survival and identification of potential biomarkers associated with tipifarnib activity.

About Tipifarnib

Tipifarnib is a potent, selective and orally bioavailable inhibitor of farnesyl transferase in-licensed from Janssen. Previously, tipifarnib was studied in more than 5,000 cancer patients and showed compelling and durable anti-cancer activity in certain patient subsets; however, no molecular mechanism of action had been determined that could explain its clinical activity across a range of solid tumor and hematologic indications. Leveraging advances in next generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura is seeking to identify those patients most likely to benefit from tipifarnib. In November 2018, the U.S. Patent and Trademark Office issued a new patent for tipifarnib as a method of treating patients with AITL, providing exclusivity in the U.S. to 2037. In March 2020, the U.S. Food and Drug Administration granted Fast Track designation to tipifarnib for the treatment of adult patients with relapsed or refractory AITL.

On December 13, 2021 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, reported that its research collaborators at the Fred Hutchinson Cancer Research Center presented nonclinical data of STRO-002 and STRO-001 in two oral presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH 2021) in Atlanta, Georgia (Press release, Sutro Biopharma, DEC 13, 2021, View Source [SID1234596951]). The research was conducted by investigators from the laboratory of Soheil Meshinchi, M.D., Ph.D., Professor, Clinical Research Division at Fred Hutchinson Cancer Research Center and Professor, Division of Pediatric Hematology-Oncology at the University of Washington School of Medicine.

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Dr. Meshinchi commented, "Using a computational approach, we have identified FOLR1, or FolRα, as an actionable target for high-risk pediatric AML; and CD74 as an actionable target in adult and pediatric AML and ALL. We further demonstrated that STR0-002 effectively targets a high-risk AML subtype and STRO-001 effectively targets AML and ALL cells that express CD74, providing promising nonclinical data for possible treatment options."

Nonclinical data was presented by Quy Le, Ph.D., Staff Scientist, Meshinchi Lab, Fred Hutchinson Cancer Research Center on Sutro’s folate receptor alpha (FOLR1 or FolRα) -targeting antibody-drug conjugate (ADC), STRO-002, as a potential therapeutic in a rare pediatric acute myeloid leukemia (AML) subtype expressing FolRα. RNA-sequencing data demonstrated that FOLR1 is uniquely expressed in CBFA2T3-GLIS2 fusion (CBF/GLIS) AML and absent in other AML subtypes and normal hematopoietic cell populations. Data from an AML cell line engineered to express FOLR1 and CBF/GLIS-transduced cord blood hematopoietic stem/progenitor cells (CB HSPCs) demonstrated high cytotoxicity of STRO-002. In FOLR1 positive and CBF/GLIS-transduced CB HSPCs xenograft models, STRO-002 demonstrated potent activity that led to complete leukemia clearance.

Nonclinical data was also presented by Quy Le, Ph.D., Staff Scientist, Meshinchi Lab, Fred Hutchinson Cancer Research Center on Sutro’s CD74-targeting ADC, STRO-001, as a potential therapeutic in AML and acute lymphoblastic leukemia (ALL). Data from AML and ALL cell lines, as well as from nonclinical xenograft models, demonstrated robust in vitro and in vivo cytotoxicity of STRO-001 on cells expressing high- to -moderate levels of CD74, with no cytotoxicity observed in cells without CD74 expression. Potent anti-leukemia activity was also demonstrated in three primary AML patient samples with varied CD74 expression levels.

Dr. Arturo Molina, Sutro’s Chief Medical Officer added, "These nonclinical data presented by collaborators at Fred Hutchinson Cancer Research Center demonstrates the potential of targeted ADCs as therapeutics for AML and ALL. These data provide additional validation for an FolRα- and CD74-antigen directed approach, as our clinical studies for STRO-002 in ovarian and endometrial cancers and STRO-001 in B cell malignancies, respectively, continue to enroll patients."