On March 13, 2023 AB Science SA (Euronext – FR0010557264 – AB) reported a case report from the initial stage of its Phase I/II study (AB18001) evaluating AB8939, a microtubule destabilizer, in patients with refractory and relapsed acute myeloid leukemia (AML) (Press release, AB Science, MAR 13, 2023, https://www.ab-science.com/ab-science-reports-a-first-complete-bone-marrow-response-in-a-relapsed-refractory-acute-myeloid-leukemia-patient-from-the-very-low-dose-arm-of-its-ab8939-phase-i-ii-clinical-trial-ab18001/ [SID1234628578]).

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 AML patient in question was in failure to prior treatment with azacitidine and presented with a MECOM gene rearrangement, which is a biomarker for resistance to standard chemotherapies that is associated with a high-risk of disease progression and inferior prognosis.

One month after the first treatment cycle (i.e., three consecutive days of AB8939 treatment) there was a drastic reduction in bone marrow blast cells (i.e., leukemia cells), from a pretreatment level of 55% to 5%(i.e., a morphologic leukemia free state). Remarkably, this response was achieved at a very low dose of AB8939, corresponding to the second step of dose increment (out of 13 potential steps) in phase I. The patient also showed excellent tolerance to AB8939, having experienced no treatment-related toxicities. At the request of the investigator, AB Science has authorized further treatment cycles of AB8939 to this patient. One month after the second treatment cycle of three consecutive days at this dose, a good response has been maintained with bone marrow blasts being at 10% (corresponding to a 5-fold reduction relative to baseline). A third treatment cycle for this patient has been initiated.

Considering the overall study to date, there have been no signs of moderate, severe or serious toxicity and approximately 50% of patients have requested further treatment cycles of AB8939 after the first cycle of treatment and a measurement at day 28.

Dr Pau Montesinos, hematologist at the La Fe University Hospital and coordinator of the Spanish group of acute myeloblastic leukemia (PETHEMA), said "It is remarkable that we rapidly observed a response in what is typically a difficult-to-treat patient population of refractory AML. We observe a clear blast count reduction for this patient and excellent tolerance so far. It is all the more noteworthy because the initial disappearance of leukemic cells was obtained after only 3 days of AB8939 treatment at a very low dose, with a good response maintained after a second 3-day cycle at this dose."

Professor Olivier Hermine, MD, President of the Scientific Committee of AB Science and member of the Académie des Sciences in France said "This preliminary clinical data provides the most encouraging signs to date that AB8939 may be well-suited for treatment of high-risk relapsed/refractory AML. AML is a serious life-threatening condition and the most common cause of leukemia-related mortality, in large part because patients develop chemoresistance to existing frontline AML drugs."

AML represents a heterogeneous group of diseases with different responses to treatment, which can be separated by genetic abnormalities. Overexpression of MECOM occurs in approximately 10% of AML patients
Page 2/4and is associated with a poor prognosis, in part due to its important role in the maintenance of leukemic stem cells (LSCs) [1]. Because of their quiescent (inactive) state, LSCs are not targeted by any antimitotic chemotherapy and can therefore re-establish the disease after therapy.

AB8939 treatment of this AML subpopulation is the subject matter of a provisional patent application filed by AB Science.

Study AB18001 is titled ‘A Phase 1/2 Study to Assess the Safety, Pharmacokinetics, and Efficacy of Daily Intravenous AB8939 in patients with Relapsed/Refractory Acute Myeloid Leukemia’. The study has a multi-stage design. The first part is a dose escalation study that aims to determine the safety and tolerability of intravenous AB8939 in patients with refractory or relapsed AML or patients with refractory myelodysplastic syndrome (MDS), and to determine the recommended dose for the second-stage dose expansion study. This dose expansion study aims to determine the schedule for a Phase 2 trial in patients with relapsed/refractory AML and to also provide an early efficacy (response rate) assessment of AB8939.

AB Science has developed an in -house, proprietary, platform of new generation synthetic microtubule destabilizer agents (MDA). To date, two of these MDAs have entered its drug development pipeline. AB8939 is being developed for hematological malignancies and is at the early clinical trials stage. A second, orally administered MDA is being developed for oncology indications, and is starting regulatory preclinical studies, which are required to initiate phase 1 clinical trials.

AB Science will host a live webcast on Thursday March 16, 2023, from 6pm to 7pm CET, to present in further detail the synthetic microtubule destabilizers platform and the on-going phase 1/2 with AB8939. Login details for this live webcast will be provided later.

About AB8939

AB8939 is a new synthetic microtubule-destabilizing drug. Preclinical data show that AB8939 has broad anticancer activity [2-4], with a notable advantage over standard chemotherapies that target microtubulesof being able to overcome P-glycoprotein (Pgp) and myeloperoxidase (MPO) mediated drug resistance. Development of drug resistance often restricts the clinical efficacy of microtubule-targeting chemotherapy drugs (for example, taxanes and vinca alkaloids); thus, AB8939 has strong potential to be developed in numerous oncology indications.

AB8939 was granted orphan drug designation for AML from the U.S. Food and Drug Administration (FDA).

AB8939 was entirely discovered by the laboratories of AB Science, which retains full ownership of intellectual rights, and is an example of AB Science’s focus on innovative drug development focused on improving patients’ lives. The first indication AB8939 is being developed for is acute myeloid leukemia (AML). Cytarabine (Ara-C) and azacytidine are standard chemotherapies for AML treatment, however, drug resistance is a major limitation to successful therapy. In vivo data from a highly resistant Ara-C patient derived xenograft (PDX) mouse model showed that AB8939, administered alone or in combination with Ara-C, increased survival relative to single agent Ara-C, with an accompanying significant reduction of blasts in blood and decrease in tumor growth. Further evidence of therapeutic potential was demonstrated using an azacytidine resistant PDX model with AB8939, administered alone or in combination with azacytidine, showing a significant reduction of blasts relative to single agent azacytidine. Moreover, while azacytidine was associated with strong treatment related hematotoxicity, AB8939 did not induce hematotoxicity throughout its 4-week treatment period.

References

[1] Paubelle E, Plesa A, Hayette S, et al. Efficacy of All-Trans-Retinoic Acid in High-Risk Acute Myeloid Leukemia with Overexpression of EVI1. Oncol Ther. 2019;7(2):121-130. Doi:10.1007/s40487-019-0095-9
Page 3/4[2 ] Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. In Vivo Assessment of the Next Generation Microtubule-Destabilizing Agent AB8939 in Patient-derived Xenograft Models of Acute Myeloid Leukemia. Blood (2019) 134 (Supplement_1): 5142.doi.org/10.1182/blood-2019-127143[3] Goubard A, Humbert M, Mansfield C, Hermine O, Dubreuil P, et al. AB8939, a Microtubule-Destabilizing Agent with Potential to Overcome Multidrug Resistance, is Active Across the Range (M0–M7) of Acute Myeloid Leukemia Subtypes. Blood (2019) 134 (Supplement_1): 5154.doi.org/10.1182/blood-2019-127021[4] Humbert M, Goubard A, Mansfield C, Hermine O, Dubreuil P, et al. Anticancer Activity of a Highly Potent Small Molecule Tubulin Polymerization Inhibitor, AB8939. Blood (2019) 134 (Supplement_1): 2075. doi.org/10.1182/blood-2019-122540

About acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) is a serious, life-threating condition and the most common cause of leukemia-related mortality, with a majority of patients facing a highly unsatisfactory prognosis. As such, AML represents an unmet medical need, with limited therapeutic options for patients who are refractory or too frail to benefit from potentially curative but highly toxic treatment, or for those patients that have relapsed following a first complete response. The prevalence of AML in western countries is around 1 per 5,000 persons, corresponding to around 100,000 cases in Europe and 60,000 in the USA. Among AML patients, it is estimated that approximately 50% of the patients will not have stem cell transplantation and will relapse. Therefore, the estimated targeted population of AB8938 in AML is around 80,000 people in Europe and the US.

On March 13, 2023 Pfizer Inc. (NYSE: PFE) and Seagen Inc. (Nasdaq: SGEN) reported that they have entered into a definitive merger agreement under which Pfizer will acquire Seagen, a global biotechnology company that discovers, develops and commercializes transformative cancer medicines, for $229 in cash per Seagen share for a total enterprise value of $43 billion (Press release, Pfizer, MAR 13, 2023, View Source [SID1234628574]). The Boards of Directors of both companies have unanimously approved the transaction.

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!

"Pfizer is deploying its financial resources to advance the battle against cancer, a leading cause of death worldwide with a significant impact on public health," said Dr. Albert Bourla, Pfizer Chairman and Chief Executive Officer. "Together, Pfizer and Seagen seek to accelerate the next generation of cancer breakthroughs and bring new solutions to patients by combining the power of Seagen’s antibody-drug conjugate (ADC) technology with the scale and strength of Pfizer’s capabilities and expertise. Oncology continues to be the largest growth driver in global medicine, and this acquisition will enhance Pfizer’s position in this important space and contribute meaningfully to the achievement of Pfizer’s near- and long-term financial goals."

Seagen expects to generate approximately $2.2 billion of revenue in 20231, representing 12% year-over-year growth, from its four in-line medicines, royalties and collaboration and license agreements. When combining the expected strong growth trajectories for these medicines with candidates that could emerge from Seagen’s pipeline, subject to clinical trial and regulatory success, Pfizer believes Seagen could contribute more than $10 billion in risk-adjusted revenues in 2030, with potential significant growth beyond 2030.

Seagen is a pioneer in ADC technology, with four of the twelve total FDA-approved and marketed ADCs using its technology industry-wide. ADCs are a transformative modality that is emerging as a powerful tool across a broad range of cancers designed to preferentially kill cancer cells and limit off-target toxicities. Seagen has developed a leadership position in ADC technologies since its founding 25 years ago, with groundbreaking and proprietary technology that is positioned for significant growth in 2023 and beyond. Seagen’s portfolio includes four approved medicines2 that are first- or best-in-class in their respective indications across solid tumors and hematologic malignancies, including three ADCs: ADCETRIS (brentuximab vedotin), PADCEV (enfortumab vedotin), and TIVDAK (tisotumab vedotin). The company also commercializes TUKYSA (tucatinib). Clinical development programs are ongoing for each of these medicines for potential new tumor types or expanded indications in earlier lines of therapy, with catalysts expected annually through 2027.

Seagen is also poised to expand the impact of its therapeutic approach with its broad and deep pipeline that includes eleven new molecular entities, many with the potential to treat large patient populations and all with global commercial rights.3 The proposed acquisition is also expected to enable for combination potential across both the Seagen and Pfizer pipelines and will leverage Pfizer’s protein engineering and medicinal chemistry capabilities to advance Seagen’s ADC technology to unlock potential novel target combinations and next-generation biologics.

Seagen is also advancing innovative technologies capable of potentially generating multiple Investigational New Drug Applications (INDs), including next-generation linker/payload technologies for ADCs and other innovative antibody platforms that directly engage the immune system to destroy tumors, such as bi-specific antibodies.

"Pfizer shares our steadfast commitment to patients, and this combination is a testament to the passion, dedication and talent of the Seagen team to achieve our mission to discover, develop, and commercialize transformative cancer medicines that make a meaningful difference in people’s lives," said David Epstein, Seagen Chief Executive Officer. "The proposed combination with Pfizer is the right next step for Seagen to further its strategy, and this compelling transaction will deliver significant and immediate value to our stockholders and provide new opportunities for our colleagues as part of a larger science-driven, patient-centric, global company."

Today, Pfizer Oncology has an industry-leading portfolio of 24 approved innovative cancer medicines that generated $12.1 billion in 2022 revenues, including the best-selling therapies for metastatic breast cancer and prostate cancer. Pfizer’s in-line portfolio is focused on four broad, key areas: breast cancer, genitourinary cancer, hematology and precision medicine, complemented by an extensive pipeline of 33 programs in clinical development. The proposed combination with Seagen would double Pfizer’s early-stage oncology clinical pipeline.

"Over the past decade we’ve taken bold new approaches to translating scientific research into effective medicines for people living with cancer, and we have pioneered several breakthroughs in breast cancer, genitourinary cancer, hematological malignancies and precision medicine," said Chris Boshoff, Chief Development Officer Oncology and Rare Disease, Pfizer. "The addition of Seagen’s world-leading ADC technology will position us at the forefront of innovative cancer care, and strongly complements our existing portfolio across both solid tumors and hematologic malignancies. We believe the combination of our teams, and respective areas of strength and global footprints will allow us to realize Seagen’s potential and advance even more potential breakthroughs to patients with cancer."

Pfizer expects to finance the transaction substantially through $31 billion of new, long-term debt, and the balance from a combination of short-term financing and existing cash. The transaction is expected to be neutral to slightly accretive to adjusted diluted earnings per share (EPS)4 in the third to fourth full year post close. Pfizer expects to achieve nearly $1 billion in cost efficiencies in the third full year after the completion of the transaction.

The companies expect to complete the transaction in late 2023 or early 2024, subject to fulfillment of customary closing conditions, including approval of Seagen’s stockholders and receipt of required regulatory approvals.

Pfizer’s financial advisor for the transaction is Guggenheim Securities, LLC, with Wachtell, Lipton, Rosen & Katz acting as Pfizer’s legal advisor. Centerview Partners LLC is serving as Seagen’s financial advisor and provided a fairness opinion to Seagen’s Board of Directors with Sullivan & Cromwell LLP serving as its legal advisor. MTS Health Partners also provided financial advice to Seagen.

Investor Call Details

Pfizer Inc. invites Pfizer investors and the general public to view and listen to a webcast of a live conference call with investment analysts at 8 a.m. EDT on Monday, March 13, 2023.

To view and listen to the webcast visit Pfizer’s web site at www.pfizer.com/investors or directly at View Source;LangLocaleID=1033&GroupID=Onyx. Information on accessing and pre-registering for the webcast will be available at www.pfizer.com/investors beginning today. Participants are advised to pre-register in advance of the conference call.

You can listen to the conference call by dialing either (800) 456-4352 in the United States or Canada or (785) 424-1086 outside of the United States and Canada. The password is "68017." Please join the call five minutes prior to the start time to avoid operator hold times.

The transcript and webcast replay of the call will be made available on Pfizer’s web site at www.pfizer.com/investors within 24 hours after the end of the live conference call and will be accessible for at least 90 days.

On March 13, 2023 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to develop and launch the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, reported that it is aware that the Federal Deposit Insurance Corp. has taken control of Silicon Valley Bank ("SVB") (Press release, Outlook Therapeutics, MAR 13, 2023, View Source [SID1234628573]).

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!

Outlook Therapeutics does not hold any deposits or investments at SVB.

On March 13, 2023 NightHawk Biosciences, Inc. (the "Company") reported that it has entered into Amendment No. 5 dated March 11, 2023 ("Amendment No. 5") to the Rights Agreement dated March 11, 2018, as amended by Amendment No. 1 thereto ("Amendment No. 1") dated March 8, 2019, Amendment No. 2 thereto ("Amendment No. 2") dated March 10, 2020, Amendment No. 3 thereto ("Amendment No. 3") dated March 8, 2021, and Amendment No. 4 thereto ("Amendment No. 4") dated March 11, 2022 (collectively, the "Rights Agreement") by and between the Company and Continental Stock Transfer & Trust Company, as rights agent (Filing, 8-K, NightHawk Biosciences, MAR 13, 2023, View Source [SID1234628572]). Under the terms of Amendment No. 5, the expiration date of the Company’s stockholder rights plan has been extended to March 11, 2024, or such earlier date that the Company redeems or exchanges the rights as described in the Rights Agreement

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!

A copy of Amendment No. 5 is attached as Exhibit 4.6 to this Current Report on Form 8-K and is incorporated by reference herein. A copy of the Rights Agreement as originally executed is included as Exhibit 4.1 to this Current Report on Form 8-K, Amendment No. 1 is included as Exhibit 4.2 to this Current Report on Form 8-K, Amendment No. 2 is included as Exhibit 4.3 to this Current Report on Form 8-K, Amendment No. 3 is included as Exhibit 4.4 to this Current Report on Form 8-K, and Amendment No. 4 is included as Exhibit 4.5 to this Current Report on Form 8-K and such agreements are incorporated herein by reference. The foregoing summary of Amendment No. 5 and the Rights Agreement are qualified in their entirety by reference to Exhibits 4.1, 4.2, 4.3, 4.4, 4.5 and 4.6

Item 3.03. Material Modification to Rights of Security Holders

The information set forth in Item 1.01 of this Current Report on Form 8-K is incorporated into this Item 3.03 by reference.

On March 13, 2023 Nektar Therapeutics (Nasdaq: NKTR) reported a statement confirming that it does not have any accounts at Silicon Valley Bank, and it does not hold any cash deposits or securities at Silicon Valley Bank (Press release, Nektar Therapeutics, MAR 13, 2023, View Source [SID1234628571]). At December 31, 2022, the company had approximately $505 million in cash and investments in marketable securities.

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!