On February 24, 2022 Invitae (NYSE: NVTA), a leading medical genetics company, reported financial and operating results for the fourth quarter and year ended December 31, 2021 (Press release, Invitae, FEB 24, 2022, View Source [SID1234608968]).

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Invitae’s (NVTA) mission is to bring comprehensive genetic information into mainstream medical practice to improve the quality of healthcare for billions of people. www.invitae.com (PRNewsFoto/Invitae Corporation)

"2021 was another year of industry leading growth and the addition of almost 1 million patients onto the Invitae platform, providing further evidence that the Invitae vision and one-of-a-kind testing, digital health and data network are ushering in the era of genomic health management," said Sean George, Ph.D., co-founder and CEO of Invitae. "Looking into 2022, we intend to maintain our focus on driving that shift to a healthcare ecosystem underscored by genomic information and management, while demonstrating operational excellence and charting a clear path towards operating cash flows."

Full Year and Fourth Quarter 2021 Financial Results

Generated revenue of $460.4 million in 2021, including $126.1 million in the fourth quarter.
Reported billable volume of 1.17 million in 2021, including 327,000 in the fourth quarter.
Total active healthcare provider accounts in 2021 totaled 18,458, more than 50 percent growth since the beginning of 2020.
Active pharma and commercial partnerships grew to 178, an increase of approximately 170 percent since the beginning of 2020 driving continued revenue growth from Invitae’s data and data services platform to pharma, health system and software and services partners.
Total patient population is more than 2.5 million with over 62 percent available for data sharing.
Achieved gross profit of $111.8 million in 2021, including $30.0 million in the fourth quarter. Non-GAAP gross profit was $168.4 million in 2021, and $46.0 million in the fourth quarter.
Total operating expense, which excludes cost of revenue, for the full year 2021 was $503.4 million. Operating expense for the fourth quarter of 2021 was $244.6 million. Non-GAAP operating expense was $771.1 million for the full year 2021, and $215.7 million in the fourth quarter.

Net loss for the full year 2021 was $379.0 million, or a $1.80 net loss per share. For the fourth quarter of 2021, Invitae reported a net loss of $205.1 million, or a $0.90 net loss per share. Non-GAAP net loss was $654.3 million, or a $3.10 non-GAAP net loss per share in 2021. For the fourth quarter of 2021, Invitae reported a non-GAAP net loss of $184.7 million, or a $0.81 non-GAAP net loss per share.

At December 31, 2021, cash, cash equivalents, restricted cash and marketable securities totaled $1.06 billion as compared with $1.25 billion as of September 30, 2021. Net increase in cash, cash equivalents, restricted cash, and marketable securities was $695 million in 2021, and a net decrease of $196.7 million for the fourth quarter. Cash burn was $195.6 million in the fourth quarter of 2021. Cash burn for the quarter would have been $186.1 million excluding the cash paid for acquisitions.

Guidance
The company has issued 2022 annual revenue guidance of year-over-year revenue growth of 40 percent, or approximately $640 million. New guidance categories for 2022 include gross margin and cash burn measures. Gross margin for 2022 is expected to be between 42-45 percent with cash burn, including cash used for acquisition-related activities, expected to be in the range of $600-$650 million in 2022, a more than $200 million year-over-year reduction.

Webcast and Conference Call Details
Management will host a conference call and webcast today at 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time to discuss financial results and recent developments. To access the conference call, please register at the link below:

View Source

Upon registering, each participant will be provided with call details and a conference ID.

The live webcast of the call and slide deck may be accessed here or by visiting the investors section of the company’s website at ir.invitae.com. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the company’s website.

On February 24, 2022 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing potentially curative therapies leveraging CRISPR-based technologies, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2021 (Press release, Intellia Therapeutics, FEB 24, 2022, View Source [SID1234608967]).

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"We began 2022 with strong momentum, executing against our strategic priorities for the advancement of our CRISPR-based pipeline and platform. We continued to make steady progress across our multiple clinical programs. In addition, we nominated two new development candidates – NTLA-2003 and NTLA-6001. Notably, we are looking forward to sharing additional data from the landmark study of NTLA-2001 next week," said Intellia President and Chief Executive Officer John Leonard, M.D. "In parallel, we continue to propel our own scientific innovation, as well as leverage external capabilities from across the industry to generate the next wave of clinical candidates. As part of this strategy, we completed several important transactions to further bolster our industry-leading genome editing toolbox and pipeline. Intellia is well-positioned to extend its leadership position as we aim to harness the full potential of genomic medicines."

Fourth Quarter 2021 and Recent Operational Highlights

In Vivo Program Updates

NTLA-2001 for ATTR amyloidosis: NTLA-2001 is the first investigational CRISPR-based therapy to be systemically delivered to edit genes inside the human body and has the potential to be the first single-dose treatment for transthyretin (ATTR) amyloidosis. Delivered with the Company’s in vivo lipid nanoparticle (LNP) technology, NTLA-2001 offers the possibility of halting and reversing the disease by driving a deep, potentially lifelong reduction in transthyretin (TTR) protein after a single dose. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party for this program, and Regeneron Pharmaceuticals, Inc. (Regeneron).
Intellia will be hosting a virtual investor event on February 28, 2022, at 4:30 p.m. ET to present additional interim clinical data from the ongoing Phase 1 study of NTLA-2001 in patients with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). Data to be presented will come from all four ATTRv-PN dose cohorts in Part 1, the single-ascending dose portion, and include safety and serum TTR reduction for Cohorts 3 and 4, as well as an early look at durability across all cohorts. The Company remains on track to initiate Part 2, a single-cohort expansion, in the polyneuropathy arm in the first quarter of 2022.
Intellia continues to dose patients in the cardiomyopathy arm of the Phase 1 study with NTLA-2001. In December 2021, Intellia initiated dosing in new dose-escalation cohorts in patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM) as part of the expanded Phase 1 study. Enrollment across both ATTRv-PN and ATTR-CM patient populations is expected to complete in 2022.
NTLA-2002 for HAE: NTLA-2002 leverages Intellia’s proprietary in vivo LNP delivery technology to knock out the KLKB1 gene in the liver with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of hereditary angioedema (HAE). This investigational approach aims to prevent attacks for people living with HAE by providing continuous suppression of plasma kallikrein activity following a single dose and to eliminate the significant treatment burden associated with currently available HAE therapies.
In December 2021, Intellia announced the first patient was dosed with NTLA-2002. The first-in-human study is expected to evaluate the safety, tolerability and activity of NTLA-2002 in adults with Type I or Type II HAE.
The Company anticipates presenting interim data from the Phase 1/2 study in the second half of 2022. The data are expected to characterize the emerging safety and activity profile of NTLA-2002, and to potentially demonstrate preliminary proof of concept.

NTLA-3001 for AATD-associated lung disease: NTLA-3001 is a wholly owned, first-in-class, CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of alpha-1 antitrypsin deficiency (AATD)-associated lung disease. It is designed with the aim to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. This approach seeks to eliminate the need for sub-optimal weekly IV infusions of A1AT augmentation therapy or lung transplant in severe cases.
Intellia continues to conduct Investigational New Drug (IND)-enabling activities for NTLA-3001, with plans to file an IND or IND-equivalent in 2023.
NTLA-2003 for AATD-associated liver disease: NTLA-2003 is a wholly owned in vivo knockout development candidate for the treatment of AATD-associated liver disease. It is designed to inactivate the SERPINA1 gene responsible for the production of abnormal A1AT protein in the liver. This approach aims to halt the progression of liver disease and eliminate the need for liver transplant in severe cases.
Today, Intellia announced the nomination of a new development candidate, NTLA-2003, for treatment of AATD-associated liver disease. The Company is advancing towards IND-enabling activities for this program.
Ex Vivo Program Updates

NTLA-5001 for AML: NTLA-5001 is an autologous T cell receptor (TCR)-T cell therapy engineered to target the Wilms’ Tumor 1 (WT1) antigen for the treatment of all genetic subtypes of acute myeloid leukemia (AML).
In the fourth quarter of 2021, Intellia initiated screening of patients in the Phase 1/2a study of NTLA-5001 for patients with AML. The Company has begun enrolling patients and expects to dose its first patient in the coming weeks. Later this year, the Company plans to provide guidance around timing of the first expected data readout, with the goal of demonstrating clinical proof of concept for its TCR-based platform.
NTLA-6001 for CD30+ Lymphomas: NTLA-6001 is Intellia’s wholly owned allogeneic CAR-T development candidate targeting CD30 for the treatment of CD30-expressing hematologic cancers, including relapsed or refractory classical Hodgkin’s Lymphoma (cHL).
Today, Intellia announced the nomination of its first ex vivo allogeneic development candidate, NTLA-6001, for CD30-expressing hematologic cancers, including cHL. NTLA-6001 is developed using Intellia’s proprietary allogeneic cell engineering platform, which leverages a novel combination of sequential gene edits. Preclinical data presented on its differentiated allogeneic engineering platform showed allogeneic T cells were shielded from immune rejection, both host T and natural killer (NK) cell attack.
Intellia is advancing towards IND-enabling activities and plans to present preclinical data leading to the development of NTLA-6001 at an upcoming scientific conference in 2022.
Research and Corporate Updates

Modular Platform and Pipeline Expansion: Intellia is expanding its industry-leading genome editing platform and scientific leadership through editing, delivery and cell engineering innovations that may enable broader in vivo and ex vivo applications.
Following the nomination of NTLA-2003, Intellia plans to advance at least one new in vivo development candidate by the end of 2022.
The Company plans to highlight additional advances to its proprietary technology capabilities, including both genome editing and delivery tools, at upcoming scientific conferences in 2022.
Collaboration Updates
In February, the Company executed a licensing and collaboration agreement with ONK Therapeutics Ltd. (ONK) for the development of allogeneic CRISPR-edited NK cell therapies for the treatment of cancer. The agreement grants ONK a non-exclusive license to Intellia’s proprietary ex vivo CRISPR/Cas9-based genome editing platform and its LNP-based delivery technologies and exclusive rights to certain guide RNAs for development of up to five NK cell therapies. ONK will be responsible for preclinical and clinical development for the engineered NK cell therapies covered under the agreement. In addition, the agreement grants Intellia options to co-develop and co-commercialize up to two products worldwide with rights to lead commercialization in the U.S.
In December 2021, the Company executed a licensing and collaboration agreement with Kyverna Therapeutics (Kyverna) for the development of KYV-201, an allogeneic CD19 CAR-T cell investigational candidate for the treatment of select autoimmune diseases. This is a novel approach aimed at targeting CD19 for inflammatory diseases as compared to traditional oncology indications. Kyverna will lead and fund preclinical and clinical development for KYV-201 and, as part of the agreement, Intellia granted Kyverna rights to use its proprietary ex vivo CRISPR/Cas9-based allogeneic platform in exchange for an equity stake in Kyverna. Intellia will be eligible to receive certain development and commercial milestone payments, as well as low- to mid-single-digit royalties on potential future sales and may choose to exercise an option to lead U.S. commercialization for KYV-201 under a co-development and co-commercialization agreement.
In October 2021, the Company executed a strategic collaboration with SparingVision to develop novel genomic medicines utilizing Intellia’s proprietary CRISPR/Cas9 technology for the treatment of ocular diseases. In addition, Intellia received an equity stake in SparingVision. As part of the collaboration, Intellia will receive an option for exclusive U.S. commercialization rights for product candidates arising from two of three collaboration targets, eligibility for development and commercial milestone payments, as well as royalties on potential future sales of products arising from the collaboration. The companies will additionally research and develop novel self-inactivating AAV vectors and LNP-based approaches to address delivery of CRISPR/Cas9 genome reagents to the retina.
Corporate Updates
In February, Intellia completed the acquisition of Rewrite Therapeutics, Inc. (Rewrite), a private biotechnology company focused on advancing novel DNA writing technologies. Rewrite’s DNA writing technology may enable a range of precise editing strategies. These include targeted corrections, insertions, deletions and the full range of single-nucleotide changes, which could provide new ways to edit disease-causing genes and broaden the therapeutic potential for genomic medicines.
In February, the Company announced a lease agreement to develop a 140,000-square-foot manufacturing facility in Waltham, Massachusetts, to support the manufacturing of key components for its CRISPR-based investigational therapies. The new manufacturing facility will be Good Manufacturing Practice (GMP) compliant and support both the preclinical through commercial supply for key components of Intellia’s CRISPR-based therapies. Additionally, this facility, in combination with existing capabilities and partnerships, will provide capacity and capabilities in support of Intellia’s expanding pipeline and commercial readiness.
Upcoming Events

The Company will participate in the following events during the first quarter of 2022:

AAAAI Annual Meeting, February 25-28, Phoenix
Cowen Healthcare Conference, March 7, Virtual
Barclays Capital Global Healthcare Conference, March 15, Miami
Guggenheim Healthcare Talks Genomic Medicines and Rare Disease Day, March 31, Virtual
Upcoming Milestones

The Company has set forth the following for pipeline progression:

NTLA-2001 for ATTR amyloidosis:
Report additional interim data from Phase 1 study on February 28
Initiate Part 2, a single-dose expansion cohort, of the Phase 1 study of NTLA-2001 in Q1 2022
Complete enrollment of Phase 1 study for both ATTRv-PN and ATTR-CM subjects in 2022
NTLA-2002 for HAE: Present interim data from Phase 1/2 study in 2H 2022
NTLA-3001 for AATD: Plan to file an IND or IND-equivalent in 2023
NTLA-5001 for AML: Continue to enroll patients in Phase 1/2a study in 2022
NTLA-6001 for CD30+ Lymphomas: Plan to present preclinical data at an upcoming scientific conference in 2022
Pipeline Expansion:
Advance at least one new in vivo development candidate by the end of 2022
Advance additional novel platform capabilities in 2022

Fourth Quarter and Full-Year 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $1,086.0 million as of December 31, 2021, compared to $597.4 million as of December 31, 2020. The increase was driven by net proceeds of $648.3 million from a follow-on offering in the third quarter of 2021, $45.3 million of net proceeds from the Company’s "At the Market" (ATM) agreement, $43.1 million in proceeds from employee-based stock plans, and $6.3 million of funding for cost-sharing agreements received from Regeneron. These increases were offset in part by cash used to fund operations of approximately $254.7 million.
Collaboration Revenue: Collaboration revenue increased by $6.3 million to $12.9 million during the fourth quarter of 2021, compared to $6.6 million during the fourth quarter of 2020. This increase was primarily driven by $5.8 million in revenue recorded in 2021 from our joint venture with AvenCell.
R&D Expenses: Research and development expenses increased by $32.9 million to $71.2 million during the fourth quarter of 2021, compared to $38.2 million during the fourth quarter of 2020. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs and expansion of the development organization.
G&A Expenses: General and administrative expenses increased by $11.3 million to $22.1 million during the fourth quarter of 2021, compared to $10.8 million during the fourth quarter of 2020. This increase was primarily related to employee related expenses, including stock-based compensation of $3.8 million.
Net Loss: The Company’s net loss was $81.2 million for the fourth quarter of 2021, compared to $42.2 million during the fourth quarter of 2020.

Conference Call to Discuss Fourth Quarter and Full-Year 2021 Results

The Company will discuss these results on a conference call today, Thursday, February 24, at 8:00 a.m. ET.

To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.
Please visit this link for a simultaneous live webcast of the call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at intelliatx.com, beginning on February 24, at 12:00 p.m. ET.

On February 24, 2022 Genmab A/S (Nasdaq: GMAB) and Seagen Inc. (Nasdaq: SGEN) reported that it will present preliminary data from the innovaTV 207 global, open-label, multicenter phase 2 trial of tisotumab vedotin (TIVDAK) as a monotherapy in patients with squamous cell carcinoma of the head and neck (SCCHN) who experienced disease progression on or after a first-line platinum-containing regimen and a checkpoint inhibitor (Press release, Genmab, FEB 24, 2022, View Source [SID1234608965]). Early results showed tisotumab vedotin demonstrated a manageable safety profile and promising preliminary antitumor activity in this patient population with the primary endpoint of confirmed objective response rate (ORR) per investigator, achieved by 16 percent of patients (95% CI: 5.5 to 33.7). Findings will be presented as part of a plenary session at the American Society for Radiation Oncology (ASTRO) 2022 Multidisciplinary Head and Neck Cancers Symposium on February 25.

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"There is a significant unmet need for additional treatment options for patients diagnosed with squamous cell carcinoma of the head and neck that has progressed despite the use of chemotherapy," said David S. Hong, M.D., deputy chair of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and lead investigator of the innovaTV 207 clinical trial. "These preliminary data provide important insight into the safety of tisotumab vedotin in this tumor type and demonstrate the value of exploring this potential use further in the innovaTV 207 trial."

The SCCHN cohort of the innovaTV 207 trial enrolled 31 patients with a median age of 65 (range 47 to 78) years whose disease progressed on or after systemic therapy. Patients received 2 milligrams (mg)/kilogram (kg) tisotumab vedotin (maximum dose: 200 mg per infusion) intravenously on day one of each 21-day cycle. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS) per investigator and overall survival (OS). DCR per investigator was 58.1 percent (95% CI: 39.1 to 75.5), median PFS was 4.2 months (95% CI: 2.7 to 4.8), median follow-up was 10.0 months (95% CI: 8.5 to 13.1) and median OS was 9.4 months (95% CI: 8.1 to 11.8). Adverse events were consistent with the known safety profile of tisotumab vedotin: twenty-one (67.7%) patients developed Grade ≥3 treatment-emergent adverse events (TEAEs); most commonly (≥10% of patients) anemia (16.1%), pneumonia (12.9%), and dyspnea (12.9%). Incidence of treatment-emergent serious adverse events (SAEs) was 51.6%, and incidence of treatment-related SAEs was 6.5% (grade 3 hemoptysis [n=1] and grade 3 post-procedural hemorrhage [n=1]).

See TIVDAK U.S. Important Safety Information, including Boxed Warning, below.

"We recognize the high medical need for additional treatment options for patients with head and neck cancers," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "These initial data results are encouraging and underscore the importance of our ongoing clinical trial program that will assess the potential utility of tisotumab vedotin in various cancers."

For more information about the ongoing phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov (Identifier: NCT03485209).

"The presentation of these preliminary data represents another step forward in our work to advance the tisotumab vedotin development program," said Roger Dansey, M.D., Chief Medical Officer, Seagen. "In partnership with Genmab, we will continue to recruit additional patients for trials to further investigate tisotumab vedotin in patients with squamous cell carcinoma of the head and neck, including its potential use as a combination therapy."

About the innovaTV 207 Trial
The phase 2 innovaTV 207 clinical trial evaluates the activity, safety, and tolerability of tisotumab vedotin in selected solid tumors with high tissue factor (TF) expression. The trial is a global, multicenter, open label basket trial which will enroll an estimated 532 adult patients with relapsed, locally-advanced or metastatic disease in separate tumor-specific cohorts. The primary endpoint of the trial is confirmed ORR per investigator, defined as the proportion of patients who achieve a confirmed complete or partial response. Key secondary endpoints include confirmed and unconfirmed ORR, DCR, duration of response, PFS, OS, safety and tolerability. For more information about the phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov (Identifier: NCT03485209).

About Tisotumab Vedotin
Tisotumab vedotin-tftv (TIVDAK) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Seagen’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggests that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

In September 2021, the U.S. Food and Drug Administration granted accelerated approval for tisotumab vedotin (TIVDAK) in patients with previously treated recurrent or metastatic cervical cancer. TIVDAK is the first and only approved ADC for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Indication
TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Important Safety Information

BOXED WARNING: OCULAR TOXICITY
TIVDAK caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion. Withhold TIVDAK until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Warnings and Precautions
Ocular Adverse Reactions occurred in 60% of patients with cervical cancer treated with TIVDAK across clinical trials. The most common were conjunctival adverse reactions (40%), dry eye (29%), corneal adverse reactions (21%), and blepharitis (8%). Grade 3 ocular adverse reactions occurred in 3.8 % of patients, including severe ulcerative keratitis in 3.2% of patients. One patient experienced ulcerative keratitis with perforation requiring corneal transplantation. Cases of symblepharon were reported in patients with other tumor types treated with TIVDAK at the recommended dose. In innovaTV 204, 4% of patients experienced visual acuity changes to 20/50 or worse including 1% of patients who experienced a visual acuity change to 20/200. Of the patients who experienced decreased visual acuity to 20/50 or worse, 75% resolved, including the patient who experienced decreased visual acuity to 20/200.

Refer patients to an eye care provider for an ophthalmic exam including visual acuity and slit lamp exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care to reduce the risk of ocular adverse reactions. Promptly refer patients to an eye care provider for any new or worsening ocular signs and symptoms. Withhold dose, reduce the dose, or permanently discontinue TIVDAK based on the severity of the adverse reaction.

Peripheral Neuropathy (PN) occurred in 42% of cervical cancer patients treated with TIVDAK across clinical trials; 8% of patients experienced Grade 3 PN. PN adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (11%), peripheral sensorimotor neuropathy (5%), motor neuropathy (3%), muscular weakness (3%), and demyelinating peripheral polyneuropathy (1%). One patient with another tumor type treated with TIVDAK at the recommended dose developed Guillain- Barre syndrome. Monitor patients for signs and symptoms of neuropathy. For new or worsening PN, withhold, dose reduce, or permanently discontinue TIVDAK based on the severity of PN.

Hemorrhage occurred in 62% of cervical cancer patients treated with TIVDAK across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients. Monitor patients for signs and symptoms of hemorrhage. For patients experiencing pulmonary or CNS hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage recurrence. After resolution, either resume treatment or permanently discontinue TIVDAK.

Pneumonitis: Severe, life-threatening, or fatal pneumonitis can occur in patients treated with antibody-drug conjugates containing vedotin, including TIVDAK. Among patients with cervical cancer treated with TIVDAK across clinical trials, 2 patients (1.3%) experienced pneumonitis, including 1 patient who had a fatal outcome.

Monitor patients for pulmonary symptoms of pneumonitis. Infectious, neoplastic, and other causes for symptoms should be excluded through appropriate investigations.

Withhold TIVDAK for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue TIVDAK in all patients with Grade 3 or 4 pneumonitis.

Embryo-Fetal Toxicity: TIVDAK can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TIVDAK and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with TIVDAK and for 4 months after the last dose.

Adverse Reactions
In the innovaTV 204 clinical trial (n=101), serious adverse reactions occurred in 43% of patients; the most common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN, sepsis, constipation, and pyrexia (each 3%). Fatal adverse reactions occurred in 4% of patients who received TIVDAK, including septic shock, pneumonitis, sudden death, and multisystem organ failure (each 1%).

Adverse reactions leading to permanent discontinuation occurred in 13% of patients receiving TIVDAK; the most common (≥3%) were PN (5%) and corneal adverse reactions (4%). Adverse reactions leading to dose interruption occurred in 47% of patients; the most common (≥3%) were PN (8%), conjunctival adverse reactions (4%), and hemorrhage (4%). Adverse reactions leading to dose reduction occurred in 23% of patients; the most common (≥3%) were conjunctival adverse reactions (9%) and corneal adverse reactions (8%).

The most common (≥25%) adverse reactions, including laboratory abnormalities, were hemoglobin decreased (52%), fatigue (50%), lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia (39%), epistaxis (39%), conjunctival adverse reactions (37%), hemorrhage (32%), leukocytes decreased (30%), creatinine increased (29%), dry eye (29%), prothrombin international normalized ratio increased (26%), activated partial thromboplastin time prolonged (26%), diarrhea (25%), and rash (25%).

Drug interactions

Strong CYP3A4 Inhibitors: Concomitant use with strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the risk of TIVDAK adverse reactions. Closely monitor patients for TIVDAK adverse reactions.

Use in Specific Populations

Moderate or Severe Hepatic Impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Lactation: Advise lactating women not to breastfeed during TIVDAK treatment and for at least 3 weeks after the last dose.

On February 24, 2022 Galapagos NV (Euronext & NASDAQ: GLPG) reported that financial results 2021, reviews key events for the company, and provides outlook for 2022 (Press release, Galapagos, FEB 24, 2022, View Source [SID1234608964]).

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"2021 was a year of reflection, resulting in refocused R&D activities and resized spend, as well as commercial roll-out, with a major effort to launch Jyseleca throughout Europe," said Onno van de Stolpe, CEO of Galapagos. "We made excellent progress with Jyseleca and successfully completed the process of becoming Marketing Authorization Holder (MAH) in Europe for our first medicine. Improving patients’ lives is at the core of what we do, and completing our transition to a fully integrated, independent European biopharma is a major achievement to make that mission a reality for patients suffering from chronic debilitating conditions.

We received approval by the European Commission (EC), and most recently by the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain, for a second indication for Jyseleca for patients suffering from UC, and we continue to roll out Jyseleca in RA and UC throughout Europe. Furthermore, following the completion of patient enrollment in the DIVERSITY Phase 3 program with filgotinib in CD, we anticipate topline results in the first half of 2023.

Also for filgotinib, we were pleased to report on the primary endpoint with the MANTA and MANTA-RAy studies investigating the effect on semen parameters, indicating that 8.3% patients on placebo and 6.7% patients on filgotinib had a 50% or more decline in sperm concentration at week 13.

In 2021, we also made important progress across our broader inflammation pipeline, most notably with our TYK2 and SIKi programs. We observed clinical activity with our TYK2 inhibitor GLPG3667 in a Phase 1b study in Pso, and we are currently finalizing a Phase 1 dose escalation study in healthy volunteers. We reported results from the first patient studies of our SIKi program with SIK2/3 inhibitor GLPG3970. The biological activity observed in the studies in Pso and UC highlights the pioneering role we are playing to unravel the role of SIKi in inflammation, and support further development of our SIKi portfolio. We are currently working on a set of follow-up SIKi compounds with improved pharmacology and selectivity profiles, and plan to select a preclinical candidate to move into a healthy volunteer study this year.

Beyond inflammation, we discontinued further development of ziritaxestat (GLPG1690) in IPF due to the unfavorable risk/benefit profile observed by an Independent Data Monitoring Committee (IDMC) in the Phase 3 trials. This not only was a major setback for Galapagos but most importantly for patients suffering from this debilitating disease for which current treatment options remain limited.

Finally, we completed the patient recruitment in our MANGROVE Phase 2 trial with our novel CFTR2 inhibitor GLPG2737 in patients with ADPKD3, with results expected in the first half of 2023.

I am very proud of our committed teams for working tirelessly to bring novel mode of action medicines to patients, and now that my tenure at the helm of this company is drawing to an end, I could not be more honored to hand over the baton to Paul. As a co-founder and board member in the early years, Paul has a keen understanding of our roots as well as who we are today. I strongly believe that Paul’s strategic and inspirational leadership, along with his deep knowledge of both the industry and Galapagos, make him the right next CEO to deliver tremendous value to all stakeholders."

Bart Filius, President, COO and CFO of Galapagos, added: "We ended 2021 with a very strong balance sheet, providing us with the foundations for future growth. One year after receiving approval for Jyseleca in RA in Europe and Great Britain, we secured reimbursement in 14 countries, covering the major markets of Germany, France, Spain, Italy, and Great Britain. We reported €14.8 million of Jyseleca sales in Europe out of a total in-market performance of €25.7 million.

Following a strategic operational review in March 2021, we implemented a cost savings program of €150 million on a full year basis, which will take full effect in the course of 2022. Our operational cash burni in 2021 was €564.8 million, within our reduced guidance. For 2022 we anticipate a further significant reduction of our cash burn and expect to land between €450 and €490 million. This includes sales for Jyseleca that we anticipate between €65 and €75 million."

Details of the financial results
After the sale of our fee-for-service business (Fidelta) to Selvita on 4 January 2021, we only have one remaining reporting segment. The results of Fidelta, including the impact of the 2021 sale, are presented as "Net profit from discontinued operations" in our consolidated income statements for the years 2021 and 2020.

Revenues from continuing operations
Our net revenues from continuing operations in 2021 amounted to €484.8 million compared to €478.1 million in 2020.

We reported net sales of Jyseleca in 2021 amounting to €14.8 million, which reflects the sales booked by Galapagos after the country-by-country transition from Gilead.

Collaboration revenues amounted to €470.1 million in 2021, compared to €478.1 million last year. The revenue recognition linked to the upfront consideration and milestone payments in the scope of the collaboration with Gilead for filgotinib, amounted to €235.7 million in 2021 (€228.1 million in 2020). The revenue recognition related to the exclusive access rights for Gilead to our drug discovery platform amounted to €230.6 million in 2021 (€229.6 million last year). Additionally we have recognized royalty income from Gilead for Jyseleca for €3.8 million in 2021 (compared to €16.2 million in 2020, which was mainly from income related to upfront payments from a distribution agreement for the commercial launch of filgotinib in Japan).

Our deferred income balance at 31 December 2021 includes €1.8 billion allocated to our drug discovery platform that is recognized linearly over 10 years, and €0.6 billion allocated to the filgotinib development that is recognized over time until the end of the development period.

Results from continuing operations

We realized a net loss from continuing operations of €125.4 million in 2021, compared to a net loss of €311.0 million in 2020.

We reported an operating loss amounting to €165.6 million in 2021, compared to an operating loss of €178.6 million in 2020.

Cost of sales related to Jyseleca net sales in 2021 amounted to €1.6 million.

Our R&D expenditure in 2021 amounted to €491.7 million, compared to €523.7 million in 2020. This decrease was primarily due to the winding down of the programs with ziritaxestat (IPF), MOR106 (atopic dermatitis), and GLPG1972 (OA), and reduced spend on our other programs. This was partly offset by cost increases for our filgotinib and Toledo (SIKi) programs, on a yearly comparison basis.

Our S&M and G&A expenses were respectively €70.0 million and €140.9 million in 2021, compared to respectively €66.5 million and €118.8 million in 2020. This increase was primarily due to an increase in personnel costs resulting from an increase in headcount and other operating expenses mainly driven by the commercial launch of filgotinib in Europe. This increase was partly offset by higher cost recharges from us to Gilead in the scope of our commercial cost sharing for filgotinib in Europe.

Other operating income (€53.7 million in 2021 vs €52.2 million last year) slightly increased, mainly driven by higher grant income.

We reported a non-cash fair value gain from the re-measurement of initial warrant B issued to Gilead, amounting to €3.0 million in 2021 (€3.0 million in 2020), mainly due to the decreased implied volatility of the Galapagos share price and its evolution between 31 December 2020 and 31 December 2021.

Net other financial income in 2021 amounted to €39.6 million, compared to net other financial loss of €134.2 million in 2020. Net other financial income in 2021 was primarily attributable to €57.2 million of currency exchange gains on our cash and cash equivalents in U.S. dollars, and to €8.8 million of net interest expenses. The other financial expenses also contained the effect of discounting our long term deferred income of €9.3 million.

Results from discontinued operations
The net profit from discontinued operations in 2021 consisted of the gain on the sale of Fidelta, our fee-for-services business, for €22.2 million.

Group net results
We reported a group net loss in 2021 of €103.2 million, compared to a group net loss of €305.4 million in 2020.

Cash position
Current financial investments and cash and cash equivalents totaled €4,703.2 million on 31 December 2021, as compared to €5,169.3 million on 31 December 2020 (including the cash and cash equivalents included in the assets as classified as held for sale).

Total net decrease in cash and cash equivalents and current financial investments amounted to €466.1 million in 2021, compared to a net decrease of €611.5 million in 2020. This net decrease was composed of (i) €564.8 million of operational cash burn, offset by (ii) €6.8 million positive changes in (fair) value of current financial investments and €59.9 million of mainly positive exchange rate differences, (iii) €3.3 million of cash proceeds from capital and share premium increase from exercise of subscription rights in 2021, and (iv) €28.7 million cash in from disposal of subsidiaries.

Our balance sheet on 31 December 2021 included R&D incentives receivables from the French government (Crédit d’Impôt Rechercheiv) and from the Belgian government, for a total of €144.0 million.

Outlook 2022

Early in 2022, we announced the appointment of Dr. Paul Stoffels as successor to our co-founder and current CEO Onno van de Stolpe, effective 1 April 2022. Paul is widely recognized as an inspirational industry leader with exceptional R&D and global executive experience, with an outstanding track record of accelerated product development in biotech and pharma through insightful acquisitions and strategic partnerships.

In 2022, we expect reimbursement decisions in most key European markets for Jyseleca in UC. In Japan, collaboration partner Gilead expects a decision on the potential approval for Jyseleca in UC in the first half of 2022, which potentially could add a second indication for Jyseleca in this market.

Early this year, the EMA announced that its Pharmacovigilance Risk Assessment Committee (PRAC) started an Article 20 specific pharmacovigilance procedure to investigate the safety data for all JAK inhibitors following recent results from the ORAL Surveillance study with tofacitinib4 as well as the data from an observational study with baricitinib5. Following initiation of this procedure, all JAKi MAHs will be invited to submit evidence and we will continue to work with the EMA. The European Commission has asked the EMA to give its opinion by 30 September 2022.

Within our broader inflammation portfolio, we expect the read out from a Phase 1b trial with JAK1 inhibitor GLPG0555 in osteoarthritis and from multiple Phase 1 trials in healthy volunteers. We aim to progress our TYK2 inhibitor GLPG3667 into a Phase 2 program, following the dose escalation Phase 1 study currently being finalized, also taking into account the current regulatory and competitive landscape for TYK2 as a class. We aim to advance selected compounds with optimized pharmacology and selectivity from our SIKi portfolio into the clinic. Within our fibrosis portfolio, we anticipate starting a Phase 2 trial with chitinase inhibitor GLPG4716 in IPF.

For 2022 we anticipate a further significant reduction of our cash burn and expect to land between €450 and €490 million. This includes sales for Jyseleca that we anticipate between €65 and €75 million.

We believe our strong cash balance affords us the opportunity to develop our pipeline through internal as well as externally sourced assets. We expect our scientific expertise, strong leadership, and growing commercial Jyseleca franchise to propel us forward as we rebuild a differentiated pipeline of novel mode of action drug candidates to help patients in need of new treatment options.

Annual report 2021

Galapagos is currently finalizing its financial statements for the year ended 31 December 2021. Our independent auditor has confirmed that its audit procedures, which are substantially completed, have not revealed any material corrections required to be made to the financial information included in this press release. Should any material changes arise during the audit finalization, an additional press release will be issued. Galapagos expects to be able to publish its fully audited annual report for the full year 2021 on or around 24 March 2022.

Conference call and webcast presentation

Galapagos will conduct a conference call open to the public tomorrow, 25 February 2022, at 14:00 CET / 8 AM ET, which will also be webcasted. To participate in the conference call, please call one of the following numbers ten minutes prior to commencement:

CODE: 5438549

A question and answer session will follow the presentation of the results. Go to www.glpg.com to access the live audio webcast. The archived webcast will also be available for replay shortly after the close of the call.

Financial calendar

24 March 2022 Publication Annual Report 2021 and 20-F 2021
26 April 2022 Annual Shareholders’ meeting
5 May 2022 First quarter 2022 results (webcast 6 May 2022)
4 August 2022 Half Year 2022 results (webcast 5 August 2022)
3 November 2022 Third quarter 2022 results (webcast 4 November 2022)
23 February 2023 Full year 2022 results (webcast 24 February 2023)

On February 24, 2022 MilliporeSigma, the U.S. and Canada Life Science business sector of Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported the closing of the transaction to acquire Exelead, following regulatory clearances and the fulfillment of other customary closing conditions, for approximately USD 780 million in cash (Press release, MilliporeSigma, FEB 24, 2022, View Source [SID1234608963]). The business combination is expected to enable the Life Science business to provide its customers with comprehensive end-to-end contract development and manufacturing organization (CDMO) services across the mRNA value chain. The Life Science business plans to further invest over € 500 million to scale up Exelead’s technology over the next ten years.

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MilliporeSigma Announces Close of Exelead Acquisition

"With the addition of Exelead’s leading capabilities and highly experienced team, our Life Science business achieves an important milestone in becoming one of the leading CDMO players in mRNA vaccines and therapeutics, offering an integrated CDMO across the mRNA value chain from pre-clinical to commercial," said Matthias Heinzel, Member of the Executive Board of Merck KGaA, Darmstadt, Germany, and CEO Life Science. "mRNA holds much promise as a treatment well beyond Covid-19 and we will further invest in this technology to help realize its potential."

Exelead, a biopharmaceutical CDMO, specializes in PEGylated products and complex injectable formulations, including Lipid Nanoparticle (LNP) based drug delivery technology, which is key in mRNA vaccines and therapeutics for use in Covid-19 and many other indications. The company has experience in all development phases from pre-clinical development to commercial contract manufacturing for LNP formulations, including fill and finish. Exelead will complement the Life Science business sector’s more than 20 years’ experience in producing lipids as well as its mRNA manufacturing capabilities acquired through AmpTec in 2020. This integrated offering will accelerate the Life Science business sector’s ability to bring life-enhancing vaccines and treatments to patients faster by simplifying supply chain complexity and enhancing speed to market through its end-to-end portfolio.

Over the past two years, the Life Science business sector has made significant investments to advance traditional and novel modalities (mAb, ADC, HP-API, viral vector, and mRNA) through acquisitions and expansions. The acquisition of Exelead is another milestone to accelerate innovation in the company’s Process Solutions and Life Science Services businesses, one of the company’s three growth engines ("Big 3"), through targeted smaller to medium-sized acquisitions with high impact.

Follow MilliporeSigma on Twitter @MilliporeSigma, on Facebook @MilliporeSigma and on LinkedIn.

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