On May 12, 2023 Evotec SE (Frankfurt Stock Exchange: Prime Standard, ISIN: DE0005664809; NASDAQ: EVO) reported its Annual Report for the fiscal year 2022, as well as the qualitative Quarterly Statement for the first quarter of 2023 (Press release, Evotec, MAY 11, 2023, View Source [SID1234631595]).

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Evotec’s fully audited Annual Report 2022 "Ahead of the Curve" is now available for downloading on www.evotec.com/financial-reports. Evotec had published preliminary financial results for FY2022 already on 28 March, which have remained unchanged. The publication of the final document had to be postponed after Evotec became the victim of a criminal cyber-attack that was discovered in early April.

Evotec also published a qualitative Quarterly Statement for the first quarter of 2023 today. Since the cyber-attack was discovered after the end of the first quarter, the Company’s Q1 results remain materially unaffected and saw a very strong start to the year with several deal extensions and expansions, e.g. a multi-billion-US$ extension of the Company’s neuroscience partnership with Bristol Myers Squibb, and the announcement of new partnerships, e.g. with Janssen in the field of immune-based therapies. Scale and scope of these transactions were materially larger than in the comparable period 2022.

Guidance for FY2023 remains unchanged. Evotec expects revenues in the range of € 820 – 840 m (€ 835 – 855 m at constant fx-rates) and adj. EBITDA in the range of € 115 – 130 m (€ 125 – 140 m at constant fx-rates).

Supported by the new long-term alliance with Sandoz in the field of biosimilars that was announced earlier this week, Evotec sees itself well positioned to achieve its mid-term targets of "Action Plan 2025", i.e. revenue growth to >€ 1,000 m, adjusted EBITDA of ≥€ 300 m and unpartnered research and development expenses of >€ 100 m by 2025.

In response to the criminal cyber-attack, Evotec took immediate action to contain and remediate the attack by taking its external-facing systems offline. This was deemed necessary to protect all of the Company’s partners and stakeholders. Evotec expects a fast return to full productivity, and business recovery. However, it cannot be ruled out that there could be a potential impact on the aforementioned guidance. Management will continue to monitor the situation and provide updates in subsequent reporting.

The Company will provide the next update on the financials – including an analysis of Q1 2023 developments – with the publication of the Half-Year Report 2023 that will be published on 09 August 2023.

With the publication of the audited Annual Report 2022 made today, Evotec expects to fulfil the criteria to be reinstated by Deutsche Börse/Qontigo in the relevant stock indices (MDAX, TecDAX, Prime All Share, LTecDAX, Technology All Share and CDAX). The Company anticipates the re-entry on 19 June on the grounds of the Fast Entry evaluation due on 05 June.

On 05 June 2023, Evotec will hold an ESG Capital Markets Day and present the Company’s strategic guardrails for a resilient business that remains "ahead of the curve" – even in times of global uncertainty. The ESG Capital Markets Day will be held as a virtual and invitation-only event. A recording of the broadcast will be available on www.evotec.com in the days after the event.

On May 12, 2023 Cellectis (the "Company") (Euronext Growth: ALCLS – NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported an article in Frontiers Bioenginnering, demonstrating the efficacy of its TALEN engineered FAP UCART-cells in cancer-associated fibroblast (CAF) depletion, reduction of desmoplasia and tumor infiltration (Press release, Cellectis, MAY 11, 2023, View Source [SID1234631590]).

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Adoptive cell therapy based on chimeric antigen receptor-engineered T (CAR-T) cells has proven to be lifesaving for many cancer patients.

However, its therapeutic efficacy has so far been restricted to only a few malignancies, with solid tumors proving to be especially recalcitrant to efficient therapy. Poor intra-tumor infiltration by T cells and T cell dysfunction due to a desmoplastic, immunosuppressive microenvironment are key barriers for CAR T-cell success against solid tumors.-

Cancer-associated fibroblasts (CAFs) are critical components of the tumor stroma, evolving specifically within the tumor microenvironment (TME). The CAF secretome is a significant contributor to the extracellular matrix and a plethora of cytokines and growth factors that induce immune suppression. Together they form a physical and chemical barrier which induces a T cell-excluding ‘cold’ TME. CAF depletion in stroma rich solid tumors can thus provide an opportunity to convert immune evasive tumors susceptible to tumor-antigen CAR T-cell cytotoxicity.

Cellectis used its TALEN-based gene editing platform to engineer non-alloreactive, immune-evasive UCAR T-cells targeting the unique CAF marker Fibroblast Activation Protein, alpha (FAP) to test whether FAP UCAR T-cell pre-treatment can make ‘cold’ tumors susceptible to subsequent tumor-antigen targeting CAR T-cells. Cellectis also generated non-alloreactive CAR T-cells against the tumor associated antigen (TAA) Mesothelin which is overexpressed in most solid tumors including mesothelioma and large sub-sets of ovarian, breast, pancreatic and lung adenocarcinomas. The combination treatment strategy was tested in a pre-clinical mouse model of triple-negative breast cancer (TNBC), an aggressive, stroma-rich breast cancer sub-type with poor prognosis and very limited treatment options at present.

"Over 90% of epithelial cancers including breast, colorectal, pancreatic and lung adenocarcinomas express the CAF-specific surface marker, fibroblast activation protein α (FAP), which makes it a promising CAR T-cell target. In this study, we propose a novel and versatile approach of combination CAR T-cell therapy that can be extended to most stroma-rich cold tumors with relevant tumor-antigen targeting CAR T-cells which otherwise are recalcitrant to cell therapy", said Shipra Das, Ph.D., Senior Scientist & Team Leader at Cellectis.

Preclinical data showed that :

In a mouse xenograft model, successful implantation of injected CAFs in the tumors was confirmed by positive staining of spindle-like cells with human-specific FAP antibody, recapitulating a physiologically relevant TNBC tumor with tumor and stromal compartments.
FAP UCART-cells alone significantly reduced tumor growth.
In vitro and in vivo results show that FAP UCART-cells enable the reprogramming of the cold, stroma-rich triple negative breast cancer (TNBC) TME, making the tumor susceptible to subsequent Meso UCAR T infiltration and cytotoxicity and improving the overall antitumor activity of the treatment.
In the context of combination therapy with anti-PD1 checkpoint inhibitor, maximal anti-tumor activity and survival benefits were observed upon FAP UCAR T-cell treatment followed by Meso UCAR T-cell treatment.

On May 11, 2023 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported its financial results for the three months ended March 31, 2023, and provided a business update (Press release, Altimmune, MAY 11, 2023, View Source [SID1234631579]).

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"We are on course for mid-year initiation of IMPACT, our Phase 2b biopsy trial of pemvidutide in subjects with NASH," said Vipin K. Garg, Ph.D., President and Chief Executive Officer of Altimmune. "In our previous trials in subjects with non-alcoholic fatty liver disease (NAFLD), we observed remarkable reductions in liver fat content and markers of liver inflammation that occurred rapidly after treatment. This leads us to believe that the IMPACT trial has the potential to show a statistically significant impact on the key endpoints of NASH resolution and fibrosis improvement. We also believe pemvidutide may distinguish itself from other candidates in development for NASH because of its demonstrated reductions in both liver fat content and body weight. This is important, because many NASH patients suffer not only from the complications of liver disease but also from the underlying obesity, a principal driver of NASH. In addition, we eagerly await top-line 48-week results from our MOMENTUM obesity trial anticipated in the fourth quarter of 2023, which we expect will demonstrate continued weight loss beyond the robust levels reported at the 24-week interim analysis. We believe pemvidutide could be an important treatment option for patients with obesity, if approved, particularly those with NAFLD and dyslipidemia, conditions that are highly prevalent in these patients. We also look forward to the top-line results of our Phase 2 trial of HepTcell in CHB, which we expect to announce in the first quarter of 2024."

Recent Highlights and Anticipated Milestones

Pemvidutide

Positive interim data readout from 24-week MOMENTUM Phase 2 obesity trial in March 2023
Mean weight loss of 10.7% and 9.4% at the 2.4 mg and 1.8 mg doses, respectively, at Week 24, compared to mean weight loss of 1.0% in the placebo group.
Approximately 50% of subjects achieved 10% or more weight loss and approximately 20% of subjects achieved 15% or more weight loss at both the 2.4 mg and 1.8 mg doses at Week 24.
Robust reductions in waist circumference, serum lipids and blood pressure, surrogates of reduced cardiovascular risk.
Higher adverse event discontinuation rates observed at the 2.4 mg dose can be mitigated by allowance for dose reduction in Phase 3 trials.
Initiation of IMPACT Phase 2b NASH trial expected mid-2023
This Phase 2b biopsy-driven NASH trial will be conducted at approximately 60 sites in the U.S., with Dr. Stephen Harrison, Medical Director, Pinnacle Research, and Adjunct Professor of Medicine, Oxford University, serving as the principal investigator.
190 subjects with and without diabetes are planned to be randomized 1:2:2 to pemvidutide 1.2 mg, pemvidutide 1.8 mg, or placebo.
The key endpoints will be NASH resolution and fibrosis improvement after 24 weeks of treatment, with subjects followed for an additional 24 weeks to a total of 48 weeks for assessment of safety and additional biomarker responses.
Dose reduction will be allowed for subjects who experience GI intolerance.
The trial is expected to commence mid-2023 with top-line results expected in the first quarter of 2025.
HepTcell

Completed enrollment in the Phase 2 clinical trial in CHB
The multicenter clinical trial, which is being conducted at 26 sites in North America, Europe and Southeast Asia, enrolled approximately 80 previously untreated subjects with inactive CHB and low levels of hepatitis B surface antigen (HBsAg).
Subjects were randomized 1:1 to HepTcell or placebo.
The primary endpoint is virological response, defined as a 1-log or greater reduction or clearance of HBsAg; secondary endpoints include changes in the levels of hepatitis B virus (HBV) DNA, pre-genomic RNA and other markers of virologic response.
Data readout is expected in the first quarter of 2024 after all subjects complete the 6-month course of treatment.
Financial Results for the Three Months Ended March 31, 2023

Cash, cash equivalents and short-term investments totaled $165.8 million as of March 31, 2023.
Research and development expenses were $17.2 million for the three months ended March 31, 2023, compared to $15.1 million in the same period in 2022. The expenses for the quarter ended March 31, 2023 included $8.7 million in direct costs related to development activities for pemvidutide and $2.1 million in direct costs related to development activities for HepTcell.
General and administrative expenses were consistent period-over-period at $4.5 million and $4.4 million for the three months ended March 31, 2023 and March 31, 2022, respectively.
Interest income for the three months ended March 31, 2023 was $1.7 million as compared to a negligible amount in the three months ended March 31, 2022.
Net loss for the three months ended March 31, 2023 was $20.1 million, or $0.40 net loss per share, compared to a net loss of $19.4 million, or $0.44 net loss per share, in the same period in 2022.
Conference Call Information:

Date: Thursday, May 11, 2023
Time: 8:30 am EDT
Webcast: To listen, the conference call will be webcast live on Altimmune’s Investor Relations website at View Source
Dial-in: To participate or dial-in, register here to receive the dial-in numbers and unique PIN to access the call.

Following the conclusion of the call, the webcast will be available for replay on the Investor Relations page of the Company’s website at www.altimmune.com. The Company has used, and intends to continue to use, the IR portion of its website as a means of disclosing material non-public information and for complying with disclosure obligations under Regulation FD.

About Pemvidutide
Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and NASH. Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, leading to rapid reductions in levels of liver fat. Pemvidutide incorporates the EuPort domain, a proprietary technology that increases its serum half-life for weekly dosing while likely slowing the entry of pemvidutide into the bloodstream, which may improve its tolerability.

About HepTcell
HepTcell is a novel, investigational, immunotherapeutic comprised of nine synthetic peptides representing conserved HBV sequences formulated with IC31, a TLR9-based adjuvant from Valneva SE. The HBV-directed peptides are designed to drive T cell responses against all HBV genotypes towards a functional cure for chronic HBV in patients of diverse genetic backgrounds.

On May 11, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported that the first patient has been dosed in the Company’s Phase 1/2a trial evaluating narazaciclib combined with letrozole in recurrent metastatic low-grade endometrioid endometrial cancer (LGEEC) (Press release, Onconova, MAY 11, 2023, View Source [SID1234631578]). Narazaciclib is a multi-kinase inhibitor targeting CDK 4, CDK 6, and other kinases important for cell proliferation and motility. Preliminary data from the trial’s Phase 1 portion are expected in 4Q 2023.

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Endometrial cancer arises in the uterine lining and is the most common cancer of the female reproductive organs. Endometrioid endometrial cancer is the most common subtype of endometrial cancer, accounting for approximately 75% of cases. Data from prior randomized and single-arm trials have demonstrated the anti-cancer activity of letrozole combined with CDK 4/6 inhibition in recurrent endometrial cancer1-3. Currently, there is no health authority-approved CDK 4/6 inhibitor for the treatment of endometrial cancer.

"Improved treatment options for recurrent LGEEC are urgently needed, as the CDK 4/6 inhibitors currently used off-label for this indication are marked by limitations related to safety, tolerability, and treatment resistance," said Bhavana Pothuri, M.D., Professor, Department of Obstetrics and Gynecology at NYU Grossman School of Medicine and Director, Gynecologic Oncology Research; Perlmutter Cancer Center and Principal Investigator of the trial. "Narazaciclib’s kinase inhibitory profile suggests it can overcome each of these limitations thanks to reduced activity against kinases whose inhibition is associated with bone marrow toxicity and diarrhea, and increased activity against those implicated in pro-tumor immune suppression and cancer cell survival. This hypothesis is supported by data from in vitro and murine cancer models, and I look forward to its continued evaluation in the ongoing Phase 1/2a trial."

Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, "Our recurrent LGEEC program provides an opportunity to establish narazaciclib as a best-in-class therapy in an indication where clinical proof-of-concept for its mechanism of action has been demonstrated. We, therefore, view the program as a key avenue for value creation and look forward to our Phase 1/2a trial’s preliminary data readout expected later this year."

About the Phase 1/2a Trial

The Phase 1/2a trial is an open-label, multicenter study evaluating narazaciclib in combination with letrozole as a second or third-line treatment for patients with recurrent metastatic LGEEC. Both narazaciclib and letrozole are administered orally with a continuous daily dosing schedule. The trial begins with a Phase 1 dose escalation phase before moving to a Phase 2 expansion cohort designed to enroll approximately 30 patients. The primary objective of the Phase 1 portion of the trial is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in order to determine a recommended Phase 2 dose (RP2D) of the combination. The primary objective of the Phase 2 portion will be to evaluate the efficacy of the combination at the RP2D, as measured by progression-free survival at 24 weeks. The estrogen/progesterone receptor status of participants will be recorded as part of an exploratory objective. The trial will be conducted at sites including NYU Langone Health, the site of the Principal Investigator of the study, sites affiliated with MD Anderson Cancer Center, and U.S. Oncology Research sites.

References

1. Mirza MR. ESMO (Free ESMO Whitepaper) Virtual Congress 2020. Abstr. LBA28.

2. Konstantinopoulos PA, et al.; 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022. Phoenix, AZ

3. Colon-Otero G, Zanfagnin V, Hou X, et al. ESMO (Free ESMO Whitepaper) Open. 2020 Oct;5(5):e000926. doi: 10.1136/esmoopen-2020-000926.

On May 11, 2023 Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported its financial results for the quarter ended March 31, 2023 and provided a business update (Press release, Aptevo Therapeutics, MAY 11, 2023, View Source [SID1234631577]).

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First Quarter Highlights

Raised $9.7 million in non-dilutive funding, extending cash runway beyond 12 months
A portion of the proceeds was used to fully repay the existing debt facility on the Company’s balance sheet
The Company achieved this by closing a transaction for the complete sale of all future IXINITY deferred payments and a portion of IXINITY milestones to XOMA Corporation
Announced plans to initiate its Phase 2 program in the second half of 2023 to further evaluate APVO436, a bispecific CD3xCD123 ADAPTIR molecule, in combination with venetoclax and azacytidine in frontline and relapsed/refractory venetoclax treatment naïve patients with acute myeloid leukemia (AML). The trial design will be informed by the positive Phase 1 results announced at ASH (Free ASH Whitepaper) in December 2022
Dosed the first patient in the Company’s Phase 1 trial evaluating ALG.APV-527 intended for the treatment of solid tumors, potentially including, but not limited to, breast, colon, lung and pancreatic, which are likely to express the 5T4 antigen
ALG.APV-527 is a bispecific antibody designed to target cancer cells by activating both T-cells and natural killer cells and is intended to bind to tumor-specific antigens while sparing healthy cells and maximizing immune response
Introduced pipeline candidate, APVO711, a PD-L1 x CD40 compound with a dual mechanism of action that includes a checkpoint inhibitor that blocks the T cell inhibitory pathway while also stimulating antigen presenting cells
APVO711 has the potential to fight a range of solid malignancies such as head and neck squamous cell carcinoma, melanoma, and carcinomas of the lung, gastrointestinal tract and colon
The Company filed a provisional patent for APVO711 in January 2023
"As promised, momentum on all fronts continued into the first quarter of this year. Clinical plans continue to progress for our APVO436 Phase 2 program in the treatment of AML, and we continue to advance our ALG.APV-527 Phase 1 trial for the treatment of multiple solid tumor types after dosing the first patient in early February. This trial is ongoing, and we expect preliminary results in the second half of this year, said Marvin White, President and Chief Executive Officer at Aptevo. "We are particularly excited about our new molecule, APVO711. It’s dual mechanism of action has the potential to both stimulate cells that fight cancer and as a checkpoint inhibitor, block the pathways that cause it to spread. APVO711 was also built with safety in mind and is specifically designed to overcome the clinical toxicity commonly associated with CD40."

He added, "On the business front, we were very pleased to raise $9.7 million in non-dilutive capital by completing the sale of all future IXINITY deferred payments and a portion of IXINITY milestones to XOMA Corporation. We used part of the proceeds to fully repay our debt and are very pleased to say that Aptevo is a debt-free company," Mr. White concluded.

First Quarter 2023 Financial Results

Cash Position: Aptevo had cash and cash equivalents as of March 31, 2023 totaling $25.3 million.

Royalty Revenue: Royalty revenue for the period covered by this report reflects revenue recorded only in the first quarter of 2022 due to our Amendment to Royalty Purchase Agreement with HCR. As a result of the amendment, we ceased reporting as royalty revenue, royalties paid by Pfizer to HCR related to Pfizer’s sales of RUXIENCE (rituximab-pvvr). The last quarter for which we reported this royalty revenue was Q1 2022. The Amendment was effected to address a Nasdaq compliance matter and had the additional effect of eliminating the requirement to report all future Pfizer non-cash royalty revenue and extinguishing the liability that we recorded upon the initial sale of the royalties to HCR. RUXIENCE is a registered trademark of Pfizer.

Research and Development Expenses: For the three months ended March 31, 2023, research and development expenses decreased by $0.7 million, to $4.2 million from $4.9 million for the three months ended March 31, 2022. The decrease was primarily due to lower spending on APVO436 as we concluded enrollment in our dose expansion phase of the clinical trial and working toward the launch of Phase 2, following promising clinical data reported in the fourth quarter of 2022. Additionally, we had lower consulting and employee related costs compared to the same period in prior year. The decrease was partially offset by higher spending on the ALG.APV-527 Phase 1 clinical trial.

General and Administrative Expenses: For the three months ended March 31, 2023, general and administrative expenses decreased by $0.3 million, to $3.6 million from $3.9 million for the three months ended March 31, 2022. The decrease is primarily due to lower employee and consulting costs.

Other Income (Expense): Other income (expense) consists primarily of a gain related to sale of nonfinancial asset, costs related to debt extinguishment, accrued exit fees on debt, non-cash interest on financing agreements, and interest on debt.

Other Expense, Net

Other expense, net was $0.1 million and $2.3 million for the three months ended March 31, 2023 and 2022, respectively. Beginning in Q2 2022, we no longer record non-cash interest expense due to our Amendment to the Royalty Purchase Agreement in the second quarter of 2022, which eliminated the liability related to the sale of royalties. This contributed $1.7 million of the decrease during the period. The rest of the decrease is primarily due to lower interest expense recorded in Q1 2023 on our MidCap term loan due to principal paydown.

Gain Related to Sale of Non-Financial Asset

We recorded $9.7 million in other income for the three months ended March 31, 2023, due to the sale of the deferred payments and milestones to XOMA during the quarter. We did not have any such gain for the comparative period in the prior year.

Discontinued Operations: Income from discontinued operations was $1.0 million and $0.2 million for the for the three months ended March 31, 2023 and 2022, respectively. For the three months ended March 31, 2023, we collected $0.5 million in deferred payments from Medexus related to IXINITY sales and $0.2 million related to funds released from escrow from the sale of Aptevo BioTherapeutics in 2020. Additionally, we received $0.3 million related to the sale of hyperimmune business Saol as a result of the collection of certain accounts receivable. For the three months ended March 31, 2022, we collected $0.2 million in deferred payments from Medexus related IXINITY sales.

Net Income (Loss): Aptevo had a net income of $2.8 million or $0.39 per share for the period ended March 31, 2023, compared to a net loss of $7.7 million or $1.55 per share for the corresponding period in 2022.