On November 6, 2023 Compugen Ltd. (Nasdaq: CGEN) (TASE:CGEN) a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported data presented at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), held on November 1-5, 2023 (Press release, Compugen, NOV 6, 2023, View Source [SID1234637017]). The results reinforce previous data suggesting COM701 mediated anti-tumor activity in patients typically not responding to immunotherapy. For the first time, initial data showing the association between baseline PVRL2 levels and clinical benefit was presented, suggesting the potential of PVRL2 as a predictive biomarker for clinical benefit in certain indications helping to inform future direction of studies with a biomarker driven strategy.

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"We were delighted to present at SITC (Free SITC Whitepaper) clinical data which reinforces data previously presented, suggesting that COM701 mediated anti-tumor activity in patients typically not responding to immunotherapy", said Anat Cohen-Dayag, Ph.D., President, and CEO of Compugen. "The clinical benefit shown in patients with platinum resistant ovarian cancer was associated with infiltration of T cells into the tumor microenvironment and independent of baseline inflammatory status, suggesting a COM701 mediated mechanism of action. In addition, we presented data in metastatic breast cancer, another indication in which patients who typically do not respond to immunotherapy, derived clinical benefit from COM701 combinations."

Dr. Cohen-Dayag added, "We are also excited with the progress we have made on the predictive biomarker front, consistent with our deep understanding of the biology of PVRIG. At SITC (Free SITC Whitepaper), we presented for the first time initial data suggesting an association between baseline levels of the ligand for PVRIG, PVRL2, and clinical benefit, suggesting PVRL2 may be a predictive biomarker to help enrich for patients who may derive clinical benefit from our COM701 combinations. We are continuing to assess this association in our ongoing proof-of-concept study in platinum resistant ovarian cancer in which biopsies are mandatory. Acknowledging the competitive evolving platinum resistant ovarian cancer treatment landscape, we believe a biomarker that would help to enrich for patients who could derive clinical benefit, and together with durable responses and safety profile of our triplet combination, could support us in building a unique development path of our triplet regimen in these patients."

Stephanie Gaillard, M.D., Ph.D. Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, and first author of the study added, "Durable partial responses lasting more than 16 months is clinically meaningful in patients with high grade epithelial platinum resistant ovarian cancer. While the numbers are small, typical median duration of response is 3-4 months with standard chemotherapy and 6.9 months reported in patients treated with the recently approved antibody drug conjugate. What is also notable is the favorable safety profile of this triple blockade of PVRIG, TIGIT and PD-1. I look forward to the results of the ongoing proof-of-concept study evaluating the combination of COM701, COM902 and pembrolizumab in platinum resistant ovarian cancer patients."

Ecaterina Dumbrava, M.D., The University of Texas MD, Anderson Cancer Center, Houston, Texas, and first author of the study continued, "Following treatment with COM701 in combination with nivolumab, it is encouraging to see a complete response of greater than 21 months and a partial response of 10 months in patients with metastatic breast cancer, which is notoriously difficult to treat. Both patients had low PD-L1 expression and low tumor mutation burden at baseline. The patient who responded for 21 months and remains on treatment at the time of data cut off is HER 2 negative, a tumor which is considered as immune cold. The patient who responded for 10 months had a triple negative breast cancer, which is the fastest growing and most aggressive kind of breast cancer. It is also notable that the combination has favorable safety and tolerability profile. These data warrant further investigation of this combination with the addition of the anti-TIGIT, COM902, in tumors not typically responding to immunotherapy to address a significant unmet medical need."

Poster presentation details:

The posters are available on the publication section of Compugen’s website.

Title: Immune modulation and baseline biomarker correlation with clinical benefit following treatment with COM701 + nivolumab +/- BMS-986207 in patients with platinum resistant ovarian cancer
First Author: Gady Cojocaru

Title: The combination of COM701 + nivolumab demonstrates preliminary antitumor activity in patients with metastatic breast cancer
First Author: Ecaterina Dumbrava

Title: Durable responses with triple blockade of the DNAM-1 axis with COM701 + BMS-986207 + nivolumab in patients with platinum resistant ovarian cancer
First Author: Stephanie Gaillard

The data will be discussed during the Compugen’s Q3 conference call tomorrow November 7, 2023 at 8:30AM ET. To access the live conference call by telephone, please dial 1-866-744-5399 from the U.S., or +972-3-918-0644 internationally. The call will be available via live webcast through Compugen’s website, located at the following link.

Following the live webcast, a replay will be available on the Company’s website.

On November 6, 2023 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), reported financial results for the quarter ended September 30, 2023, and recent business highlights (Press release, Coherus Biosciences, NOV 6, 2023, View Source [SID1234637016]):

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RECENT BUSINESS HIGHLIGHTS

CIMERLI

CIMERLI (ranibizumab-eqrn) net product sales increased in the third quarter 2023 to $40.0 million compared to $26.7 million in the second quarter. CIMERLI sales have exceeded 100,000 doses since commercial launch on October 3, 2022, and CIMERLI held a 29% share of the overall ranibizumab market in the third quarter 2023.
UDENYCA

UDENYCA (pegfilgrastim-cbqv) net product sales increased in the third quarter 2023 to $33.0 million compared to $31.7 million in the second quarter. Market share grew to 16.5% in the third quarter 2023, an increase of 4.3 market share percentage points compared to the prior quarter.
As of late September, more than 250 accounts had ordered the autoinjector (AI) presentation of UDENYCA, which was launched commercially on May 22, 2023. Coherus anticipates demand will continue to rise with significantly improved commercial and Medicare Advantage formulary coverage in the fourth quarter of 2023 and in 2024.
Coherus resubmitted the Biologics License Application (BLA) Supplement for UDENYCA ONBODY, the company’s on-body injector presentation of UDENYCA (pegfilgrastim-cbqv), to the U.S. Food and Drug Administration (FDA) for review on October 4, 2023. This followed the completion and satisfactory resolution of the FDA’s review of inspection findings at a third-party filler, which was the only issue identified in the FDA’s September 21, 2023 Complete Response Letter (CRL). Coherus anticipates potential approval for the UDENYCA ONBODY in late 2023 or by early 2024.
LOQTORZI (toripalimab-tpzi)

On October 27, 2023, the FDA approved LOQTORZI (toripalimab-tpzi) in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced nasopharygeal carcinoma (NPC), and as monotherapy for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after platinum-containing chemotherapy. Commercial launch is expected in the first quarter of 2024.
Coherus presented new mechanism of action data for LOQTORZI at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) and at the 38th Annual Meeting of Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper).
YUSIMRY

Coherus launched YUSIMRY, a Humira biosimilar, with a citrate-free and sting-free formulation delivered via a state-of-the-art autoinjector July 3, 2023. YUSIMRY is now available for sale nationwide through retail, mail order and specialty pharmacy channels.
Surface Oncology Acquisition and Novel Immuno-oncology Pipeline

On September 8, 2023, Coherus announced the closing of its acquisition of Surface Oncology, Inc. The acquisition significantly advanced Coherus’ next-generation immuno-oncology pipeline focused on the tumor micro-environment with clinical stage anti-IL-27 and anti-CCR8 monoclonal antibody development programs.
Coherus presented new preclinical data for casdozokitug, a first-in-class IL-27 antibody and CHS-114, a highly selective cytolytic CCR8 antibody at the 38th Annual SITC (Free SITC Whitepaper) meeting.
Coherus plans to file an Investigational New Drug (IND) application in first quarter of 2024 for CHS-1000, a novel ILT4-targeted antibody.
"With the approval of LOQTORZI and the closing of the Surface Oncology acquisition, Coherus has all the elements in place to realize its vision of building an innovative immuno-oncology company with a commercial-stage PD-1 inhibitor and a highly competitive, next-generation clinical I-O pipeline focused on the tumor microenvironment," said Denny Lanfear, Coherus’ Chairman and Chief Executive Officer. "Our net revenues of $74.6 million in the third quarter represent an increase of 27% compared to Q2, and our SG&A plus R&D costs year to date have declined 28% compared to the same period last year. Looking forward, we expect further revenue growth driven by CIMERLI, the UDENYCA franchise, YUSIMRY, and LOQTORZI, while holding the line on expenses and focusing on returning to profitability."

THIRD QUARTER 2023 FINANCIAL RESULTS

Net revenue was $74.6 million during the three months ended September 30, 2023 and included $33.0 million of net sales of UDENYCA, $40.0 million of net sales of CIMERLI, and $1.4 million of net sales of YUSIMRY, which was launched July 3, 2023. Net revenue for the three months ended September 30, 2022, consisting primarily of UDENYCA net sales, was $45.4 million. Net revenue was $165.7 million and $165.7 million for the nine months ended September 30, 2023 and 2022, respectively. Year to date revenues remained flat compared to the prior period primarily due to a reduction in the number of units of UDENYCA sold as well as a lower net realized price due to increased competition offset by increasing revenue from CIMERLI and YUSIMRY sales during the nine months ended September 30, 2023.

Cost of goods sold (COGS) for the three months ended September 30, 2023 and 2022 was $32.7 million and $35.2 million, respectively, and $74.4 million and $55.9 million during the nine months ended September 30, 2023 and 2022, respectively. COGS includes a mid-single digit royalty payable on net sales of UDENYCA through the first half of 2024, and 2023 COGS also includes a low to mid 50% royalty payable on gross profits of CIMERLI.

The decrease in COGS for the three months ended September 30, 2023 compared to the same period in the prior year was primarily due to the $26.0 million write-down in the third quarter 2022 of inventory at risk of expiration and due to the sale in the third quarter 2023 of certain of those UDENYCA units having a total original cost of $2.4 million but no carrying value following the write-off, partially offset by a $17.0 million increase in royalty costs and $8.4 million increase in product costs primarily driven by CIMERLI sales and the mix of products sold.

The increase in COGS for the nine months ended September 30, 2023 compared to the same period in the prior year was due to a $28.1 million increase in royalty costs primarily driven by CIMERLI sales, $3.0 million in contract modification fees with one of our manufacturers for reducing the number of UDENYCA batches to be produced, and $2.3 million in write-offs, net of recoveries for inventory that was damaged during processing. These unfavorable factors were partially offset by the factors associated with the write-down in the third quarter of 2022 noted above.

Research and development (R&D) expense for the three months ended September 30, 2023 and 2022 was $25.6 million and $45.8 million, respectively. For the nine months ended September 30, 2023 and 2022, R&D expense was $83.1 million and $170.3 million, respectively. The decline in R&D expense compared to the prior year periods primarily resulted from the reduction in scope of the toripalimab collaboration and from the recognition in the first quarter of 2022 of the $35.0 million option exercise fee paid to Junshi Biosciences to license CHS-006. R&D expense for the first nine months of 2022 also included development costs for additional presentations of UDENYCA and certain manufacturing expenses for YUSIMRY which began to be capitalized in mid 2022.

Selling, general and administrative (SG&A) expense was $48.2 million and $44.8 million during the three months ended September 30, 2023 and 2022, respectively, and $142.5 million and $144.9 million during the nine months ended September 30, 2023 and 2022, respectively. The increase in SG&A expense in the three months ended September 30, 2023 was primarily due to an increase in professional services fees associated with the acquisition of Surface Oncology that was completed in September 2023. The decline in SG&A expense in the nine months ended September 30, 2023 compared to the prior year period primarily reflects lower headcount.

Net loss for the third quarter of 2023 was $39.6 million, or $(0.41) per share on a diluted basis, compared to a net loss of $86.7 million, or $(1.11) per share on a diluted basis for the same period in 2022. Net loss for the nine months ended September 30, 2023 was $158.2 million, or $(1.79) per share on a diluted basis, compared to a net loss of $232.9 million, or $(3.00) per share on a diluted basis for the same period in 2022.

Non-GAAP net loss for the third quarter of 2023 was $26.9 million, or $(0.27) per share on a diluted basis, compared to non-GAAP net loss of $74.4 million, or $(0.96) per share on a diluted basis for the same period in 2022. Non-GAAP net loss for the nine months ended September 30, 2023 was $117.3 million, or $(1.33) per share on a diluted basis, compared to non-GAAP net loss of $187.7 million, or $(2.42) per share on a diluted basis for the same period in 2022. See "Non-GAAP Financial Measures" below for a discussion on how Coherus calculates non-GAAP net loss and a reconciliation to the most directly comparable GAAP measures.

Cash, cash equivalents and investments in marketable securities were $131.1 million as of September 30, 2023, compared to $191.7 million at December 31, 2022.

2023 Revenue and R&D and SG&A Expense Guidance

Primarily due to the delay in the timing of the planned commercial launches of the UDENYCA On-body Injector and of LOQTORZI, Coherus is lowering its guidance for 2023 net product revenue to a range of $250 to $260 million.

Coherus is lowering its guidance range for combined R&D and SG&A expenses for 2023 from $315 to $335 million to a range of $300 to $310 million. This guidance range includes $40 to $45 million of stock-based compensation expense and excludes the Surface Oncology acquisition cost as well as any potential collaboration upfront or milestone payments.

This financial guidance also excludes the effects of any potential future strategic acquisitions, collaborations or investments, the exercise of rights or options related to collaboration programs, and any other transactions or circumstances not yet identified or quantified. This guidance is subject to a number of risks and uncertainties. See Forward-Looking Statements described in the section below.

Conference Call Information
When: Monday, November 6, 2023, starting at 5:00 p.m. Eastern Time

To access the conference call, please pre-register through the following link to receive dial-in information and a personal PIN to access the live call: https://register.vevent.com/register/BI0eececfba52f4f83a7438c9f002fabc4

Please dial-in 15 minutes early to ensure a timely connection to the call.

Webcast Link: View Source

A replay of the webcast will be archived on the "Investors" section of the Coherus website at View Source

On November 6, 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 business updates and financial results for the nine-month period ending September 30, 2023 (Press release, Cellectis, NOV 6, 2023, View Source [SID1234637012]).

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On November 1st 2023, Cellectis and AstraZeneca Holdings B.V. ("AstraZeneca") entered into a joint research collaboration agreement (the "Collaboration Agreement"), pursuant to which AstraZeneca makes an upfront payment of $25 million, an investment agreement relating to an initial equity investment of $80 million (the "Initial Investment Agreement") and a non-binding memorandum of understanding relating to an additional equity investment subject to conditions set forth in the MOU of $140 millions (the "MOU").

This research collaboration will leverage Cellectis’ gene editing technologies and manufacturing capabilities to accelerate the development of next-generation therapeutics in areas of high unmet need, including oncology, immunology and rare diseases. Cellectis has exclusively reserved 25 genetic targets for AstraZeneca, from which up to 10 novel candidate products could be explored for development. Cellectis’ clinical-stage assets, UCART22, UCART123 and UCART20x22 will remain under Cellectis’ ownership and control.

Pipeline Highlights

UCART Clinical Development Programs

BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)

Cellectis will present a poster at the ASH (Free ASH Whitepaper) Annual Meeting with updated results of the Phase I BALLI-01 Trial of UCART22 (P2), an anti-CD22 allogeneic CAR T- cell product manufactured in-house, in patients with relapsed or refractory (r/r) CD22+ B-Cell acute lymphoblastic leukemia (B-ALL).

The poster presentation highlights the following data:

In vitro comparability studies suggested that UCART22 process 2 (P2) (manufactured in-house) is more potent than UCART22 process 1 (P1) (manufactured by an external CDMO), and as of July 1st, 2023, 3 patients were enrolled into the first UCART22 P2 cohort at dose level 2 (1 million cells/kg).
UCART22 P2 was administered after fludarabine, cyclophosphamide, and alemtuzumab (FCA) lymphodepletion and was well tolerated. No DLTs or ICANS was observed, and the CRS observed was Grade 1 or 2.
There was a higher preliminary response rate (67%) at dose level 2 with one million cells/kg with UCART22 P2 compared to 50% response rate with a dose 5 times higher at dose level 3 of UCART22 P1 that was manufactured by an external CDMO.
UCART22 expansion was observed in the responding patients and correlated with increases in serum cytokines and inflammatory markers.
The study continues to enroll patients at dose level 2i (2.5 million cells/kg) with UCART22 P2.

NATHALI-01 (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)

Cellectis will present a poster at the ASH (Free ASH Whitepaper) Annual Meeting with the initial preliminary results from the NATHALI-01 trial (NCT05607420), a Phase 1/2a dose-finding and expansion study evaluating UCART20x22 in r/r B-cell NHL.

The poster presentation highlights the following data:

As of July 1st, 2023, 3 patients were enrolled and treated at dose level 1 (50 million cells). Cytokine release syndrome (CRS) Grade 1 or 2 occurred in all patients, and all CRS resolved with treatment. No immune effector cell associated neurotoxicity (ICANS) or graft versus host disease (GvHD) was observed. There were no UCART20x22 dose limiting toxicities (DLTs), and there was 1 DLT in connection with CLLS52 (alemtuzumab).
All patients responded at Day 28, with 1 partial metabolic response and 2 complete metabolic responses in patients who had failed prior autologous CD19 CAR T-cell therapies.
UCART20x22 expansion correlated with increases in serum cytokine and inflammatory marker levels as well as with CRS.
These initial data support the continued study of UCART20x22 in r/r B-cell NHL.
AMELI-01 (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML)

UCART123 is an allogeneic CAR T-cell product candidate targeting CD123 and is being evaluated in patients with r/r AML in the AMELI-01 Phase 1 dose-escalation clinical study.
The AMELI-01 study is currently enrolling patients after FCA lymphodepletion in a two-dose regimen arm.
Research Data & Preclinical Programs

Cellectis announced the publication of a new research paper in Molecular Therapy – Methods & Clinical Development, demonstrating the efficacy of its TALEN-mediated gene correction of mutated PIK3CD gene in Activated phosphoinositide 3-kinase delta syndrome 1 (APDS1) T-cells.
Cellectis presented encouraging data on gene editing process using TALEN-based gene editing platform, to overcome the challenges of the "cold" tumor microenvironment in a poster at the CICON 2023 (CRI-ENCI-AACR 7th International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper)).
Cellectis presented preclinical data on MUC1-CAR T-cells to overcome key challenges of targeting solid tumors in a poster session at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s 38th Annual Meeting (SITC 2023).
Cellectis presented preclinical data on its program of gene therapy for HSPC at the European Society of Gene and Cell Therapy (ESGCT) 30th annual congress.
Cellectis presented a comprehensive analysis of TALE-BE editing determinants at the European Society of gene and Cell Therapy (ESGST) 30th annual congress.

Licensed Allogeneic CAR T-cell Development Programs

Allogene Therapeutics, Inc.’s CAR T programs utilize Cellectis technologies. ALLO-501 and ALLO-501A are anti-CD19 products that were jointly developed under a collaboration agreement between Les Laboratoires Servier ("Servier") and Allogene Therapeutics, Inc. ("Allogene") until 15 December 2022 based on an exclusive license granted by Cellectis to Servier2. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S., Allogene continues the development for this territory while Servier retains exclusive rights for all other countries. Allogene’s anti-CD70 and anti-Claudin18.2 programs are licensed exclusively from Cellectis to Allogene and Allogene holds global development and commercial rights to these programs.

Servier and Allogene: anti-CD19 programs

Allogene announced that its ALPHA2 study will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy.
Allogene announced it will have two poster presentations from the ALPHA/ALPHA2 trials focused on lymphodepletion in allogeneic cell therapy at ASH (Free ASH Whitepaper) 2023. The first poster is a comprehensive safety review of all 85 patients treated in the Phase 1 ALPHA/ALPHA2 studies in relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL) to characterize the overall safety profile when ALLO-647 is added to standard lymphodepletion. The second poster showcases translational results from ALPHA2 generated through a collaboration with MD Anderson Cancer Center. This study compared expansion kinetics among 11 allogeneic CAR T recipients treated with the ALLO-501A product candidate in the ALPHA2 trial. According to Allogene, this study revealed the impact of recipient alloreactive CD8+ T cells in allogeneic CAR T rejection and the results of this study could help define strategies to improve allogeneic CAR T expansion, persistence and efficacy.
Allogene: anti-CD70 and anti-Claudin18.2 programs

Allogene announced that the Phase 1 dose escalation TRAVERSE trial in patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies including an immune checkpoint inhibitor and a VEGF-targeting therapy is ongoing.
Allogene announced that SITC (Free SITC Whitepaper) 2023 will include a review of research which provided early validation of ALLO-182, an AlloCAR T candidate currently in the IND-enabling phase of development targeting Claudin18.2 for the treatment of patients with gastric and pancreatic cancers.
Corporate Updates

Strategic Collaboration and Investment Agreements with AstraZeneca

Under the terms of the Collaboration Agreement, AstraZeneca will leverage Cellectis’ proprietary gene editing technologies and manufacturing capabilities to design novel cell and gene therapy candidate products. As part of the Collaboration Agreement, 25 genetic targets have been exclusively reserved for AstraZeneca, from which up to 10 candidate products could be explored for development. AstraZeneca will have an option for a worldwide exclusive license on the candidate products, to be exercised before IND filing. Cellectis’ clinical-stage assets, UCART22, UCART123 and UCART20x22 will remain under Cellectis’ ownership and control.

Pursuant to the Collaboration Agreement, Cellectis’ research costs under the collaboration will be funded by AstraZeneca and Cellectis will receive an upfront payment of $25 million. Under the terms of the Collaboration Agreement, Cellectis is also eligible to receive an investigational new drug (IND) option fee and development, regulatory and sales-related milestone payments, ranging from $70 million up to $220 million, per each of the 10 candidate products, plus tiered royalties.

As a condition to the signing of the Collaboration Agreement, AstraZeneca has agreed to make an initial equity investment of $80 million in Cellectis by subscribing for 16,000,000 ordinary shares, at a price of $5.00 per share (the "Initial Investment"). The new shares are issued to AstraZeneca by the board of directors of Cellectis pursuant to the 17th resolution of Cellectis’ shareholders meeting held on June 27, 2023. Following settlement and delivery of the new shares (expected to be on November 6, 2023), AstraZeneca will own approximately 22% of the share capital, and 21% of the voting rights of the Company, will have the right to nominate a non-voting observer on the board of directors of Cellectis, and will have the right to participate pro rata in Cellectis’s future share offerings.

Additionally, the MOU contemplates that AstraZeneca will make a potential further equity investment in Cellectis of $140 million by subscribing for two newly created classes of convertible preferred shares of Cellectis: 10,000,000 "class A" convertible preferred shares and 18,000,000 "class B" convertible preferred shares, in each case at a price of $5.00 per share (the "Additional Investment"). Until they convert into ordinary shares, the "class A" convertible preferred shares would have single voting rights and would not carry any double voting right at any moment, and the "class B" would carry no voting rights except on any distribution of dividends or reserves. Both class of preferred shares would enjoy a liquidation preference (if any liquidation surplus remains after repayment of Cellectis’ creditors and of par value to all shareholders) and would be convertible into the same number of ordinary shares with the same rights as the outstanding ordinary shares. The MOU is non-binding and the Additional Investment remains to be confirmed by both parties following a consultation process with Cellectis’ works council. If confirmed, the closing of the Additional Investment will remain subject to (i) Cellectis’ shareholders’ approval at a two-thirds majority of the votes cast by voting shareholders, (ii) clearance of such investment from the French Ministry of Economy according to the foreign direct investment French regulations, and (iii) other customary closing conditions. Immediately following the Additional Investment, it is anticipated that AstraZeneca would own approximately 44% of the share capital of the Company and 30% of the voting rights of the Company (based on the number of voting rights outstanding immediately after the completion of the Initial Investment) and would have the right to nominate two directors to the board of directors of Cellectis. Further, certain business decisions are subject to AstraZeneca’s approval, including, in particular, winding up any company of the Cellectis group, issuing securities senior to or pari passu with the convertible preferred shares or any shares without offering AstraZeneca the option to purchase its pro rata share of such securities (subject to customary exceptions, including issuances under employee equity incentive plans), declaring or paying dividends, prepaying indebtedness before due, and disposing of any material assets concerning gene editing tools or manufacturing facilities and selling, assigning, licensing, encumbering or otherwise disposing of certain material IP rights.

Financial Results

The interim condensed consolidated financial statements of Cellectis, have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board ("IFRS").

On January 13, 2023, Calyxt, Cibus Global LLC (Cibus) and certain other parties named therein, entered into an Agreement and Plan of Merger (the "Merger Agreement"), pursuant to which, subject to the terms and conditions thereof, Calyxt and Cibus will merge in an all-stock transaction (the "Calyxt Merger"). As a consequence of the foregoing, Calyxt met the "held-for-sale" criteria specified in IFRS 5 and was classified as a discontinued operation until May 31, 2023.

On June 1, 2023, Calyxt and Cibus closed the merger transaction and now operate under the name Cibus, Inc. Consequently, Calyxt was deconsolidated and Calyxt’s cash, cash equivalent and restricted cash are no longer included in the Group’s cash, cash equivalent and restricted cash since June 1, 2023.

As from June 1, 2023 and the deconsolidation of Calyxt, which corresponded to the Plants operating segment, we view our operations and manage our business in a single operating and reportable segment corresponding to the Therapeutics segment. For this reason, we are no longer presenting financial measures broken down between our two reportable segments – Therapeutics and Plants. The results of Calyxt until the date of deconsolidation are isolated under "Income (loss) from discontinued operations" in the appendices of this Q3 2023 financial results press release.

Cash: As of September 30, 2023, Cellectis, had $72 million in consolidated cash, cash equivalents, and restricted cash. This compares to $95 million in consolidated cash, cash equivalents and restricted cash as of December 31, 2022. This $23 million difference mainly reflects $79 million of cash out, which include $23 million for R&D suppliers, $12 million for SG&A suppliers, $32 million for staff costs, $8 million for rents and taxes, $4 millions of reimbursement of the "PGE" loan, and a $2 million unfavorable impact on Forex partially offset by a $23 million net cash inflow from the capital raise closed in February, a $21 million net cash inflow from EIB loan, a $6 million of net cash received from research tax credit prefinancing, a $1 million cash inflow related to the grant and refundable advance from BPI, $3 millions of financial investments’ capital gain and interests, a $1 million reimbursement of social charges paid on stock options, and a $2 million net cash inflow from licenses and other cash receipts.

With cash and cash equivalents of $67.4 million as of September 30, 2023, our anticipated borrowing of €15.0 million under Tranche B of the €40.0 million Finance Contract with EIB and the $105 million from AstraZeneca’s agreements, the Company believes it has sufficient resources to continue operating for at least twelve months following the consolidated financial statements’ publication. Additionally, the MOU contemplates that AstraZeneca will make a potential further equity investment in Cellectis of $140M by subscribing for two newly created classes of convertible preferred shares of Cellectis (the "Additional Investment"). The MOU is non-binding and the Additional Investment remains to be confirmed by both parties following a consultation process with Cellectis’ works council. If confirmed, the closing of the Additional Investment will remain subject to (i) Cellectis’ shareholders’ approval at a two-thirds majority of the votes cast by voting shareholders, (ii) clearance of such investment from the French Ministry of Economy according to the foreign direct investment French regulations, and (iii) other customary closing conditions.

With cash and cash equivalents of $67.4 million as of September 30, 2023, our anticipated borrowing of €15.0 million under Tranche B of the €40.0 million Finance Contract with EIB and the $105 million from AstraZeneca’s payments under the Collaboration Agreement and the Initial Investment Agreement, the Company believes it has sufficient resources to continue operating until Q2 2025. Concurrent with the potential additional $140 million, we expect that the Company would extend its cash runway into 2026.

Revenues and Other Income: Consolidated revenues and other income were $7.2 million for the nine months ended September 30, 2023 compared to $8.4 million for the nine months ended September 30, 2022. The decrease of $1.0 million reflects the recognition of two milestones related to Cellectis’ agreement with Cytovia for $1.5 million in 2022 and a milestone of $1.0 million with another partner while recognition of revenues in 2023 is not material, and partially offset by the increase of the research tax credit for $0.6 million and the partial recognition of a grant signed with "BPI" of $0.8 million.

R&D Expenses: Consolidated R&D expenses were $62.1 million for the nine months ended September 30, 2023, compared to $76.1 million for the nine months ended September 30, 2022. The $13.9 million decrease was primarily attributable to (i) a $8.9 million decrease in personal expenses due to departures not replaced and decrease in stock-based compensation expenses consecutive to the non-achievement of certain performance obligations of October 2020 free shares plan (ii) a $5.0 million decrease in purchases, external expenses and other (from $41.4 million in 2022 to $36.4 million in 2023) mainly due to continuing internalization of our manufacturing and quality activities to support our R&D pipeline.

SG&A Expenses: Consolidated SG&A expenses were $12.1 million for the nine months ended September 30, 2023, compared to $15.8 million for the nine months ended September 30, 2022. The $3.7 million decrease primarily reflects (i) a $2.4 million decrease in purchases, external expenses and (from $9.5 million in 2022 to $7.1 million in 2023) mainly explained by the implementation of our ERP in 2022 (ii) a $1.3 million decrease in personal expenses and non-cash stock-based compensation expenses.

Net financial gain (loss): Consolidated net financial gain was $14.9 million for the nine months ended September 30, 2023, compared to 11.0 million for the nine months ended September 30, 2022. The $3.9 million increase primarily reflects (i) a $22.8 million increase of financial income, mainly attributable to the profit from Calyxt’s deconsolidation, partially offset by (ii) the loss in fair value on our retained investment in Calyxt since deconsolidation for $6.2 million, (iii) a $7.9 million decrease in the net value of Cytovia’s note receivable.

Net income (loss) from discontinued operations: Pursuant to Calyxt deconsolidation income from discontinued operation for the nine-month period ended September 30, 2023, 2023 only include five months of activity. The $2.2 million decrease in net loss from discontinued operations between the nine-month periods ended September 30, 2022 and 2023 is primarily driven by Calyxt’s $5.7M net loss in the third quarter of 2022 compared with $0 in the third quarter of 2023 as Calyxt was deconsolidated, partially offset by a 3.5M$ increase in the net loss over the first two quarters between 2022 and 2023. This $3.5M increase breaks down as follows: (i) an increase of $9.2 million of net financial loss and (ii) an increase of $1.5 million of other operating expenses, partially offset by (i) a decrease of $2.8 million of R&D expenses (from $6.3 million in 2022 to $3.5 million in 2023) and (ii) a decrease of $4.5 million of SG&A expenses (from $6.8 million in 2022 to $2.3 million in 2023).

Net Income (loss) Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $58.2 million (or $1.07 per share) for the nine months ended September 30, 2023, of which $53.2 million was attributed to Cellectis continuing operations, compared to $79.3 million (or $1.74 per share) for the nine months ended September 30, 2022, of which $72.9 million was attributed to Cellectis continuing operations. This $21.1 million decrease in net loss between the first nine months of 2023 and 2022 was primarily driven by (i) a $13.9 million decrease of R&D expenses, (ii) a $3.7 million decrease of SG&A expense, (iii) an increase of $3.9 million of the financial gain due to the deconsolidation of Calyxt compensated in part by the decrease of fair value of Cytovia’s note receivable and, (iv) a decrease of $2.2 million of loss from discontinued operations attributable to Shareholders of Cellectis. These downward impacts on the net loss were partially offset by (i) a decrease of $1.2 million of revenues and other income.

Adjusted Net Income (Loss) Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $56.8 million (or $1.05 per share) for the nine months ended September 30, 2023, compared to a net loss of $72.1 million (or $1.58 per share) for the nine months ended September 30, 2022.

Please see "Note Regarding Use of Non-IFRS Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis.

We currently foresee focusing our cash spending at Cellectis for 2023 in the following areas:

Supporting the development of our pipeline of product candidates, including the manufacturing and clinical trial expenses of UCART123, UCART22, UCART 20×22 and potential new product candidates;
Operating our state-of-the-art manufacturing capabilities in Paris (France), and Raleigh (North Carolina, USA); and
Continuing to strengthen our manufacturing and clinical departments.

On November 6, 2023 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with genetically defined cancers, reported financial results for the third quarter ended September 30, 2023, and provided a corporate update (Press release, Black Diamond Therapeutics, NOV 6, 2023, View Source [SID1234637011]).

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"We made significant progress advancing our lead program BDTX-1535 and presented positive results in patients with NSCLC from our Phase 1 clinical trial at the AACR (Free AACR Whitepaper)-NCI-EORTC Meeting and are now rapidly enrolling the dose expansion cohorts of the trial," said Mark Velleca, M.D., Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "We have a strong cash position that will allow us to reach numerous important milestones, including dose expansion data for BDTX-1535 in patients with NSCLC, dose escalation data for BDTX-1535 in patients with GBM, and initial Phase 1 data for BDTX-4933 in KRAS, NRAS, and BRAF mutated cancers with an emphasis on NSCLC."

Recent Developments & Upcoming Milestones:

BDTX-1535:

In September 2023, Black Diamond announced the dosing of the first patients in the BDTX-1535 Phase 1 clinical trial expansion cohorts. This trial is assessing overall response rate (ORR) by RECIST 1.1 and durability of response in patients with non-small cell lung cancer (NSCLC) across two cohorts: one cohort for patients with the epidermal growth factor receptor (EGFR) acquired resistance C797S mutation after progression on a third generation EGFR tyrosine kinase inhibitor (TKI), and a second cohort for patients with non-classical (intrinsic) driver mutations after progression on an EGFR TKI (NCT05256290).
In October 2023, Black Diamond presented a poster with new clinical data at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) from the dose escalation portion of the Phase 1 clinical trial of BDTX-1535 in patients with NSCLC. Data shared at this conference reflect 27 patients with advanced/metastatic NSCLC who received a range of doses spanning 25mg to 400mg once daily. These results demonstrated a favorable tolerability profile and durable responses in patients with NSCLC expressing both acquired resistance C797S and non-classical driver EGFR mutations.
Key highlights from the presentation include:
Durable clinical responses at starting dose of 100mg or above in patients with NSCLC who had multiple lines of prior therapy. Five of the 13 patients with either non-classical driver, acquired resistance C797S or complex mutations had a confirmed partial response (PR) by RECIST 1.1. Evidence of reduction in brain metastases was observed, including a patient with more than three prior therapies. Three responders continue on therapy for greater than six months (two confirmed PRs, one unconfirmed PR). One patient with confirmed PR remained on therapy for six months. Two additional patients with stable disease continue on therapy for greater than 12 months. Eradication of targeted variant alleles and significant circulating tumor DNA (ctDNA) reductions were observed for all NSCLC EGFR mutation subtypes in patients treated with BDTX-1535 across dose levels.
Favorable emerging safety profile. The majority of adverse events (AEs) at doses of 100mg and 200mg were mild or moderate, and no unexpected safety signals were identified. No dose limiting toxicities (DLTs) were observed at 200mg or below.
In October 2023, enrollment began in a Phase 0/1 "window of opportunity" clinical trial of BDTX-1535 in patients with recurrent high-grade glioma. The trial is sponsored by the Ivy Brain Tumor Center in Phoenix, Arizona and is enrolling patients prior to a planned resection. Patients achieving adequate drug levels in the gadolinium non-enhancing regions of the tumor will continue with treatment following surgery.
Black Diamond anticipates the following upcoming key milestones for BDTX-1535:
End-of-Phase 1 Meeting with the U.S. Food and Drug Administration (FDA) later this year.
Expansion cohort data in patients with non-classical driver and acquired resistance EGFR mutant NSCLC in 2024.
Phase 1 dose escalation data in patients with relapsed and recurrent GBM later this year.
Initial results from an investigator sponsored "window of opportunity" trial in patients with GBM in the second quarter of 2024.
BDTX-4933:

BDTX-4933 is an oral, brain-penetrant RAF MasterKey inhibitor designed to address oncogenic alterations in KRAS, NRAS and BRAF, while also avoiding paradoxical activation.
A Phase 1 clinical trial for BDTX-4933 was initiated in the second quarter of 2023 in patients with BRAF and select RAS/MAPK mutation-positive cancers, with an emphasis on patients with KRAS mutant NSCLC. The trial is currently in dose escalation (NCT05786924).
In October 2023, Black Diamond presented a poster at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) detailing preclinical data for BDTX-4933.
Preclinical results showed that BDTX-4933 potently and selectively inhibited the proliferation of tumor cells expressing a range of KRAS, NRAS and BRAF mutations, suggesting clear differentiation compared to other RAF inhibitors. BDTX-4933 demonstrated strong anti-tumor activity and regression across preclinical models expressing several MAPK pathway mutations, including KRAS G12D, KRAS G12V, and KRAS G13C mutant NSCLC models. BDTX-4933 exhibited high central nervous system (CNS) exposure with dose-dependent tumor growth inhibition and survival benefit in an intracranial xenograft model.
Corporate:

In September 2023, Black Diamond announced a CEO transition, appointing Chairman of the Board Mark Velleca, M.D., Ph.D. to President and Chief Executive Officer.
Financial Highlights

Cash Position: Black Diamond ended the third quarter of 2023 with approximately $144.3 million in cash, cash equivalents, and investments compared to $122.8 million as of December 31, 2022. Net cash used in operations was $18.4 million for the third quarter of 2023 compared to $16.5 million for the third quarter of 2022.
Research and Development Expenses: Research and development (R&D) expenses were $16.2 million for the third quarter of 2023, compared to $15.8 million for the same period in 2022. The increase in R&D expenses was primarily due to the advancement of the Company’s pipeline programs, BDTX-1535 and BDTX-4933.
General and Administrative Expenses: General and administrative (G&A) expenses were $7.9 million for the third quarter of 2023, compared to $6.3 million for the same period in 2022. The increase in G&A expenses was primarily due to costs related to the transition of its former President and Chief Executive Officer in the third quarter of 2023, as well as an increase in legal and other professional fees.
Net Loss: Net loss for the third quarter of 2023 was $23.0 million, as compared to $21.7 million for the same period in 2022.
Financial Guidance

Black Diamond ended the third quarter of 2023 with approximately $144.3 million in cash, cash equivalents and investments which the Company believes is sufficient to fund its anticipated operating expenses and capital expenditure requirements into the first half of 2025.

On November 6, 2023 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported financial results for the three and nine months ended September 30, 2023, and provided an update on its corporate progress (Press release, BioNTech, NOV 6, 2023, View Source [SID1234637010]).

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"Over the last quarter, we complemented our investigational pipeline with ADC candidates, initiated later-stage clinical trials and presented significant data across modalities including cancer vaccines, cell therapies, ADCs and immune checkpoint modulators. Our strategy focuses on assembling a diverse toolbox of complementary technologies to deliver novel therapies, aiming to improve the standard-of-care for cancer patients," said Prof. Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. "We combine our internal innovation engine with a high-performance partnership model to transform healthcare and improve patients’ quality of life."

Financial Review for the Third Quarter and First Nine Months of 2023

in millions €, except per share data Third Quarter 2023 Third Quarter 2022 Nine Months
2023 Nine Months
2022
Total Revenues2 895.3 3,461.2 2,340.0 13,032.3
Net Profit 160.6 1,784.9 472.4 7,155.7
Diluted Earnings per Share 0.67 6.98 1.94 27.70
Total revenues reported were €895.3 million2 for the three months ended September 30, 2023, compared to €3,461.2 million for the comparative prior year period. For the nine months ended September 30, 2023, total revenues were €2,340.0 million2, compared to €13,032.3 million for the comparative prior year period. Inventory write-downs by BioNTech’s collaboration partner Pfizer, Inc. ("Pfizer") reduced BioNTech’s revenues by €507.9 million and €615.4 million for the three and nine months ended September 30, 2023, respectively.

Cost of sales were €161.8 million for the three months ended September 30, 2023, compared to €752.8 million for the comparative prior year period. For the nine months ended September 30, 2023, cost of sales were €420.7 million, compared to €2,811.5 million for the comparative prior year period. The change was in line with decreasing COVID-19 vaccine revenues.

Research and development (R&D) expenses were €497.9 million for the three months ended September 30, 2023, compared to €341.8 million for the comparative prior year period. For the nine months ended September 30, 2023, research and development expenses were €1,205.3 million, compared to €1,027.2 million for the comparative prior year period. Research and Development expenses are mainly influenced by progressing clinical studies for pipeline candidates, the development of variant adapted as well as next generation COVID-19 vaccines and expanding R&D headcount.

General and administrative (G&A) expenses were €144.5 million for the three months ended September 30, 2023, compared to €141.0 million for the comparative prior year period. For the nine months ended September 30, 2023, G&A expenses were €386.6 million, compared to €361.8 million for the comparative prior year period. G&A expenses were mainly influenced by increased expenses for IT services as well as expanding the G&A headcount.

Income taxes were accrued in an amount of €66.8 million for the three months ended September 30, 2023, compared to €659.2 million accrued for the comparative prior year period. For the nine months ended September 30, 2023, income taxes were accrued with an amount of €50.5 million, compared to €2,625.8 million accrued for the comparative prior year period. The derived annual effective income tax rate for the nine months ended September 30, 2023, was 9.7% which is expected to change over the 2023 financial year to be in line with the updated estimated annual cash effective income tax rate of somewhere around 21% for the BioNTech Group.

Net profit was €160.6 million for the three months ended September 30, 2023, compared to €1,784.9 million for the comparative prior year period. For the nine months ended September 30, 2023, net profit was €472.4 million, compared to €7,155.7 million net profit for the comparative prior year period.

Cash and cash equivalents as well as security investments were €16,967.6 million, comprising €13,495.8 million cash and cash equivalents and €3,471.8 million security investments, respectively, as of September 30, 2023. Subsequent to the end of the reporting period, as of October 16, 2023, a payment of €565.0 million was received from BioNTech’s collaboration partner, settling BioNTech’s gross profit share for the second quarter of 2023 (as defined by the contract with Pfizer).

Diluted earnings per share was €0.67 for the three months ended September 30, 2023, compared to a diluted earnings per share €6.98 for the comparative prior year period. For the nine months ended September 30, 2023, diluted earnings per share was €1.94, compared to €27.70 diluted earnings per share for the comparative prior year period.

Shares outstanding as of September 30, 2023, were 237,715,500, excluding 10,836,700 shares in treasury.

In March 2023, BioNTech initiated a new share repurchase program pursuant to which the Company was able to purchase American Depositary Shares, or ADSs, each representing one ordinary share of the Company, in the amount of up to $0.5 billion during the remainder of 2023. During the three months ended September 30, 2023, 3,114,280 ADSs were repurchased under the share repurchase program at an average price of €97.15 ($106.923), for total consideration of €302.5 million ($333.1 million3). The trading plan for BioNTech’s 2023 program concluded on September 18, 2023.

"In the third quarter, we continued to invest in our capabilities and our portfolio of innovative product candidates while strengthening the financial position of BioNTech. About €17 billion in cash and security investments provide strategic flexibility and is a major strength, especially in these days, where financial stability is key," said Jens Holstein, CFO of BioNTech. "We updated our financial guidance for the full year 2023. In line with anticipated revenues of around €4 billion, we reduced relevant cost drivers for 2023 as we effectively manage our expenditures."

Outlook updated for the 2023 Financial Year
The Company updated its COVID-19 vaccine revenue guidance and updates its previous expense and capex guidance for the 2023 financial year:

BioNTech COVID-19 Vaccine Revenues for the 2023 Financial Year:

Initial Guidance
Mar 2023 Updated Guidance
Nov 2023
Estimated BioNTech COVID-19 vaccine revenues for the full 2023 financial year ~ €5 billion ~ €4 billion
The revenues estimate reflects expected revenues related to BioNTech’s share of gross profit from COVID-19 vaccine sales in the collaboration partners’ territories, from direct COVID-19 vaccine sales to customers in BioNTech’s territory and expected revenues generated from products manufactured by BioNTech and sold to collaboration partners.
Revenue guidance is based on various assumptions. These include, but are not limited to, expectations regarding: transitions in the purchasing environment; the timing and receipt of regulatory approvals and recommendations; the progress of vaccination campaigns; and seasonal variations in SARS-CoV-2 circulation and vaccination uptake.

Several factors drive the Company’s adjusted revenue guidance. Such factors include BioNTech’s and Pfizer’s lower than previously forecast revenue expectations for the full 2023 financial year, which take into account delays in the expected timing of regulatory approvals, as well as the effects of Pfizer’s recently-announced write-downs and other charges.

While fewer primary vaccinations and lower population-wide levels of boosting are anticipated overall compared to the same period in prior years, vaccine adaptation and seasonal trends are expected to lead to demand peaks in the autumn and winter compared to other seasons. As a result of later-than-anticipated regulatory approvals and their effect on national vaccination campaign timelines, expected sales have shifted to future periods. In general, the Company continues to remain largely dependent on revenues generated in its collaboration partner’s territories.

In addition, BioNTech’s revenues have been affected by the inventory write-downs and other charges related to COMIRNATY that were previously announced by the Company’s collaboration partner Pfizer. As a result of the Company’s continued assessment of these write-downs and other charges, the Company has determined that the charges originating on BioNTech’s end had largely already been reflected in the Company’s financial results for the 2022 financial year, and to a smaller extent, continued to be reflected during 2023. Ultimately, the initial estimate of "up to €0.9 billion" impact has been refined by the Company. The impact from the collaboration partner’s charges onto the Company’s revenues has been identified to be €0.6 billion for the nine months ended September 30, 2023 and €0.5 billion for the three months ended September 30, 2023, which is reflected in the revised revenues guidance.

Planned 2023 Financial Year Expenses and Capex4:

Initial Guidance
Mar 2023 Updated Guidance
Nov 2023
R&D expenses5 €2,400m – €2,600m €1,800m – €2,000m
SG&A expenses €650m – €750m €600m – €650m
Capital expenditures for operating activities6 €500m – €600m €200m – €300m
Estimated 2023 Financial Year Tax Assumptions:

Initial Guidance
Mar 2023 Updated Guidance
Nov 2023
BioNTech Group estimated annual cash effective income tax rate7 ~ 27% ~ 21%
The full interim unaudited condensed consolidated financial statements can be found in BioNTech’s Report on Form 6-K for the period ended September 30, 2023, filed today with the United States Securities and Exchange Commission ("SEC") and available at View Source

Endnotes

1Financial information is prepared and presented in Euros and numbers are rounded to millions and billions of Euros in accordance with standard commercial practice.

2BioNTech’s profit share is estimated based on preliminary data shared between Pfizer and BioNTech as further described in the Annual Report. Any changes in the estimated share of the collaboration partner’s gross profit will be recognized prospectively.

3Calculated applying the average foreign exchange rate for the nine months ended September 30, 2023, as published by the German Central Bank (Deutsche Bundesbank).

4Numbers reflect current base case projections and are calculated based on constant currency rates. Excluding external risks that are not yet known and/or quantifiable, including, but not limited to, the effects of ongoing and/or future legal disputes or related activity.

5Numbers include effects identified from additional collaborations or potential M&A transactions to the extent disclosed and will be updated as needed.

6Numbers exclude potential effects caused by or driven from collaborations or M&A transactions.

7Numbers exclude potential effects caused by or driven from share-based payment settlements in the course of 2023.

Operational Review and Pipeline Update for the Third Quarter 2023 and Key Post Period-End Events

COVID-19 Vaccine Marketed Products

In August, BioNTech and Pfizer received a positive opinion from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) recommending marketing authorization for the companies’ Omicron XBB.1.5-adapted monovalent COVID-19 vaccine for individuals 6 months of age and older.
In September, BioNTech and Pfizer received approval of their supplemental Biologics License Application by the U.S. Food and Drug Administration (FDA) for their Omicron XBB.1.5-adapted monovalent COVID-19 vaccine for individuals 12 years and older, and emergency use authorization for individuals 6 months through 11 years of age.
Several other national healthcare regulatory bodies, including in the United Kingdom (UK), Japan, Canada and South Korea, have approved BioNTech and Pfizer’s monovalent XBB.1.5-adapted vaccine.
In October, BioNTech and Pfizer announced an agreement between the Japanese government and Pfizer Japan Co., Ltd. to supply an additional 9 million doses of the Omicron XBB.1.5-adapted COVID-19 vaccine for the special vaccination program in Japan which started this autumn. This follows an agreement between the Japanese government and Pfizer Inc. in July to supply 20 million doses and additional supplies as needed, and an agreement announced in September to provide additional 10 million doses of the companies’ Omicron XBB.1.5-adapted COVID-19 vaccine for the special vaccination program in Japan.
Select Oncology Pipeline Highlights – Recent and upcoming trial starts and data readouts

Antibody-Drug Conjugate (ADC) Pipeline
BioNTech’s pipeline comprises several ADCs that are based on a topoisomerase I inhibitor as payload.

BNT323/DB-1303 is an HER2-targeted ADC candidate being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. ("DualityBio").

An open-label, multi-center, randomized Phase 3 clinical trial (NCT06018337) is planned to evaluate BNT323/DB-1303 versus investigator’s choice of chemotherapy in advanced or metastatic Hormone Receptor (HR)+, HER2-low breast cancer subjects whose disease has progressed on at least two lines of prior endocrine therapy (ET) or within six months of first line ET plus CDK4/6 inhibitor in the metastatic setting, and no prior chemotherapy. The study aims to enroll approximately 532 patients.
In September, clinical data from the ongoing Phase 1/2 clinical trial (NCT05150691) evaluating BNT323/DB-1303 in patients with advanced/unresectable, recurrent, or metastatic HER2-expressing solid tumors were presented at the 2023 European Congress on Gynaecological Oncology Annual Meeting. BNT323/DB-1303 showed a manageable safety profile and no new safety signals were observed. BNT323/DB-1303 demonstrated encouraging antitumor activity in patients (n=17) with advanced, recurrent or metastatic HER2-expressing endometrial cancer with an objective response rate ("ORR"; confirmed and unconfirmed) of 58.8% and disease control rate ("DCR") of 94.1%.
BNT324/DB-1311 is an ADC candidate being developed in collaboration with DualityBio.

In September, the first patient was dosed in a first-in-human, open-label Phase 1/2 clinical trial (NCT05914116) evaluating BNT324/DB-1311 in multiple advanced solid tumors.
BNT325/DB-1305 is a TROP-2-targeted ADC candidate being developed in collaboration with DualityBio.

In October, clinical data from the ongoing Phase 1/2 clinical trial (NCT05438329) in patients with advanced solid tumors were presented at the 2023 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting suggesting a manageable safety profile at lower dose levels. Encouraging preliminary activity of BNT325/DB-1305 was observed with an ORR of 30.4% (7/23), and DCR of 87.0% (20/23) (both unconfirmed) across overall study population. Encouraging efficacy signals were observed in non-small cell lung cancer (NSCLC) patients with an ORR of 46.2% (6/13) and an DCR of 92.3% (12/13) (both unconfirmed).
BNT326/YL202 is a HER3-targeted ADC candidate being developed in collaboration with MediLink Therapeutics (Suzhou) Co., Ltd. ("MediLink").

A multicenter, open-label, first-in-human Phase 1 clinical trial (NCT05653752) evaluating YL202 as a later-line treatment in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated NSCLC or HR-positive and HER2-negative breast cancer is ongoing.
Next-Generation Immune Checkpoint Immunomodulator Pipeline

BNT316/ONC-392 (gotistobart) is an anti-CTLA-4 monoclonal antibody candidate being developed in collaboration with OncoC4, Inc. ("OncoC4"). BNT316/ONC-392 (gotistobart) is designed to offer a differentiated safety profile that may allow for higher dosing and longer duration of treatment both as monotherapy and in combination with other therapies.

In November, clinical data were presented at the 2023 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting from the ongoing Phase 1/2 trial (NCT04140526) showing that BNT316/ONC-392 (gotistobart) monotherapy has a manageable safety profile. Early readout of the expansion cohort showed encouraging clinical activity in patients with immunotherapy-resistant NSCLC. A Phase 3 trial evaluating BNT316/ONC-392 (gotistobart) monotherapy in this patient population is ongoing.
A Phase 2 clinical trial (NCT05682443) is planned to evaluate the safety and efficacy of BNT316/ONC-392 in combination with lutetium Lu-177 vipivotide tetraxetan in metastatic castration resistant prostate cancer patients who have disease progressed on androgen receptor pathway inhibition.
BNT312/GEN1042 is a bispecific antibody candidate based on Genmab A/S ("Genmab")’s DuoBody technology and designed to induce conditional immune activation by crosslinking CD40 and 4-1BB positive cells.

In November, preclinical data demonstrating in vivo antitumor activity and peripheral immune modulation of a chimeric variant of BNT312/GEN1042 were presented at the 2023 SITC (Free SITC Whitepaper) Annual Meeting. These data support ongoing Phase 1/2 clinical studies evaluating the combination of BNT312/GEN1042 with pembrolizumab and chemotherapy in patients with advanced solid tumors (NCT04083599, NCT05491317).
BNT314/GEN1059 is a bispecific antibody candidate designed to boost antitumor immune responses through EpCAM-dependent 4-1BB agonistic activity. This is the fifth drug candidate under BioNTech’s collaboration with Genmab where the development costs and potential future profits will be shared equally.

In October, preclinical data characterizing the mechanism of action of BNT314/GEN1059 were presented at the 2023 ESMO (Free ESMO Whitepaper) Annual Meeting.
A first-in-human trial sponsored by BioNTech is planned to investigate the clinical safety and preliminary antitumor activity of BNT314/GEN1059 in patients with solid tumors.
Cancer Vaccines Pipeline

BNT116 is based on BioNTech’s FixVac platform, and is a wholly owned, systemically administered, off-the-shelf mRNA-based cancer vaccine candidate. This candidate is being evaluated for the treatment of advanced NSCLC.

In July, BioNTech and Regeneron Pharmaceuticals Inc. ("Regeneron") initiated a randomized, controlled Phase 2 clinical trial (NCT05557591) to evaluate BNT116 in combination with cemiplimab (Regeneron’s Libtayo) and cemiplimab alone as first-line treatment in patients with advanced NSCLC whose tumors express PD-L1 in ≥ 50% of tumor cells.
In November, clinical data from the ongoing Phase 1 clinical trial (NCT05142189) evaluating the safety, tolerability and preliminary efficacy of BNT116 alone and in combination with cemiplimab (Regeneron’s Libtayo) or chemotherapy across various cohorts of patients were presented at the 2023 SITC (Free SITC Whitepaper) Annual Meeting. BNT116 was generally well tolerated with an expected safety profile as monotherapy and in combination with cemiplimab. In heavily pretreated NSCLC patients, treatment with BNT116 with cemiplimab from cycle 3 onwards showed early clinical activity.
BNT122 (Autogene cevumeran) is an mRNA cancer vaccine candidate based on an individualized neoantigen-specific immunotherapy (iNeST) approach being developed in collaboration with Genentech, Inc. ("Genentech"), a member of the Roche Group ("Roche").

In October, the first patient was dosed in a randomized Phase 2 clinical trial (NCT05968326) evaluating the safety and efficacy of BNT122 in combination with atezolizumab (Roche’s Tecentriq) followed by adjuvant standard-of-care chemotherapy (mFOLFIRINOX) in patients with resected pancreatic ductal adenocarcinoma (PDAC) compared to chemotherapy alone. The Phase 2 study is expected to enroll 260 patients with resected PDAC, who have not received prior systemic anti-cancer treatment and showed no evidence of disease after surgery.
Cell Therapy Pipeline

BNT211 is an autologous Claudin-6 (CLDN6)-targeting chimeric antigen receptor (CAR) T cell therapy candidate that is being tested alone and in combination with a CAR-T cell Amplifying RNA Vaccine ("CARVac"), encoding CLDN6.

In October, clinical data from the ongoing Phase 1/2 clinical trial (NCT04503278) were presented at the 2023 ESMO (Free ESMO Whitepaper) Annual Meeting detailing the new dose escalation of CLDN6 CAR-T cells with and without a CLDN6-encoding mRNA vaccine for the treatment of CLDN6-positive relapsed/refractory solid tumors using an automated manufacturing process. CLDN6 CAR-T cells ± CLDN6 CARVac demonstrated encouraging signs of clinical activity. In several patients treated with CARVac, an increased persistence of cancer-specific CAR-T cells was observed. The rate of treatment-dependent adverse events was dose-dependent. After determination of the recommended Phase 2 dose, BioNTech plans to initiate a pivotal trial in germ cell tumors.
BNT221 is an autologous, fully personalized, polyspecific T-cell therapy candidate directed against selected sets of individual neoantigens. BNT221 is based on expanded neoantigen-specific memory T cells and induced naive T cells.

In October and November, first monotherapy clinical data from the ongoing first-in-human Phase 1 dose escalation clinical trial (NCT04625205) in patients with checkpoint inhibitor unresponsive or refractory metastatic melanoma were presented at the 2023 ESMO (Free ESMO Whitepaper) and SITC (Free SITC Whitepaper) Annual Meetings. These initial results showed a manageable safety profile and encouraging activity signs of tumor regression in several patients with anti-PD-1/anti-CTLA-4 pretreated advanced or metastatic melanoma.
Select Infectious Pipeline Highlights – Recent trial starts and data readouts

COVID-19-Influenza Combination mRNA Vaccine Program – BNT162b2 + BNT161

In October, BioNTech and Pfizer announced top-line results from a Phase 1/2 clinical trial (NCT05596734) evaluating the safety, tolerability and immunogenicity of mRNA-based combination vaccine candidates for influenza and COVID-19 in healthy adults 18 to 64 years of age. In the clinical trial, the vaccine candidates were compared to licensed influenza vaccines and the Pfizer-BioNTech COVID-19 Omicron BA.4/BA.5 adapted bivalent vaccine given separately at the same visit. The data from the trial demonstrated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains, as well as a safety profile consistent with the safety profile of the companies’ COVID-19 vaccine. A pivotal Phase 3 trial is expected to be initiated in the coming months.
Mpox Program – BNT166
The BNT166 vaccine candidates encode surface antigens that are expressed in the two infectious forms of the mpox virus (MPXV) with the aim to efficiently fight virus replication and infectivity. In partnership with the Coalition for Epidemic Preparedness Innovations (CEPI), BNT166 is part of BioNTech’s infectious disease vaccine programs aiming to help provide equitable access to effective and well-tolerated vaccines for high medical need indications.

In October, the first patient was dosed in a Phase 1/2 clinical trial (NCT05988203) evaluating the safety, tolerability, reactogenicity and immunogenicity of two mRNA-based multivalent vaccine candidates against mpox. The trial aims to enroll 96 healthy participants with and without prior history of known or suspected smallpox vaccination.
Corporate Update for the Third Quarter 2023 and Key Post Period-End Events

In July, BioNTech successfully completed its previously announced acquisition of InstaDeep Ltd. ("InstaDeep"), following the satisfaction of all customary closing conditions. The acquisition supports the Company’s strategy to build world-leading capabilities in Artificial Intelligence ("AI")-driven drug discovery and development. InstaDeep will operate as a UK-based global subsidiary of BioNTech. The transaction adds approximately 290 highly skilled professionals to BioNTech’s existing bioinformatics and data science workforce, including teams in AI, machine learning, bioengineering, data science, and software development.
In September, BioNTech and CEPI announced a strategic partnership to advance mRNA-based vaccine candidates with the development of BNT166 for the prevention of mpox, an infectious disease that can lead to severe, life-threatening complications. The strategic partnership aims to contribute to CEPI’s 100 Days Mission, a goal to accelerate development of well-tolerated and effective vaccines against a potential future pandemic virus so that a vaccine can be ready for regulatory authorization and manufacturing at scale within 100 days of recognition of a pandemic pathogen. This mission is spearheaded by CEPI and embraced by the G7, G20, and industry leaders. The partnership between BioNTech and CEPI could help accelerate responses to future outbreaks caused by viruses of the Orthopoxvirus viral family. CEPI will provide funding of up to $90 million to support the development of mRNA-based vaccine candidates.
Post period-end, in October, BioNTech and MediLink entered into a strategic research collaboration and worldwide license agreement to develop a next-generation ADC candidate against Human Epidermal Growth Factor Receptor 3 (HER3). Under the terms of the agreement, MediLink will grant BioNTech exclusive global rights, excluding Mainland China, Hong Kong Special Administrative Region, and Macau Special Administrative Region, for the development, manufacturing, and commercialization of one of MediLink’s ADC assets. In exchange, BioNTech will provide MediLink with an upfront payment totaling of $70 million and additional development, regulatory and commercial milestone payments potentially totaling over $1 billion. The completion of the agreement is subject to customary closing conditions.
Also, post period-end in November, BioNTech and Biotheus Inc. ("Biotheus"), announced an exclusive license and collaboration agreement under which BioNTech will have the rights to develop, manufacture and commercialize PM8002, a bispecific antibody candidate targeting PD-L1 and VEGF, globally except in Greater China, where Biotheus retains the rights to PM8002. PM8002 is currently being tested in a Phase 2/3 study in China to evaluate the efficacy and safety of the candidate as a monotherapy or in combination with chemotherapy in patients with NSCLC.
Upcoming Investor and Analyst Events

BioNTech’s Innovation Series Day will take place tomorrow, Tuesday, November 7, 2023, from 9.00 a.m. ET (3.00 p.m. CET) in Boston, USA. The event will provide an update on BioNTech’s clinical progress across its pipeline and provide a deep dive into scientific and technological innovations from its research engine. The slide presentation and audio of the webcast will be available via this link.
BioNTech’s fourth quarter and full year 2023 financial results and corporate update are scheduled for Wednesday, March 20, 2024.
Conference Call and Webcast Information

BioNTech invites investors and the general public to join a conference call and webcast with investment analysts today, November 6, 2023, at 8.00 a.m. ET (2.00 p.m. CET) to report its financial results and provide a corporate update for the third quarter of 2023.

To access the live conference call via telephone, please register via this link. Once registered, dial-in numbers and a pin number will be provided.

The slide presentation and audio of the webcast will be available via this link.

Participants may also access the slides and the webcast of the conference call via the "Events & Presentations" page of the Investor Relations section of the Company’s website at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.