On August 4, 2022 Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, reported that it will report its second quarter 2022 financial results on Thursday, August 11, 2022 and will provide a business update (Press release, Altimmune, AUG 4, 2022, View Source [SID1234617593]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Altimmune management will host a conference call at 8:30 am E.T. on August 11 to discuss financial results and provide a business update. The conference call will be webcast live on Altimmune’s Investor Relations website at View Source

Participants who would like to join the call may register here to receive the dial-in numbers and unique PIN to access the call. Shortly after the call, a replay will be available on the Investor Relations website for up to twelve months.

On August 4, 2022 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) [("Merrimack" or the "Company")] reported its second quarter 2022 financial results for the period ended June 30, 2022 (Press release, Merrimack, AUG 4, 2022, View Source [SID1234617608]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to report continued reductions in operating expenses as we remain focused on conserving cash to ensure that we have sufficient financial resources to capture future potential milestone payments from Ipsen Pharmacology and Elevation Oncology" said Gary Crocker, Chairman of Merrimack’s Board of Directors. "We will continue to monitor developments in Ipsen’s Onivyde (irinotecan liposomal injection) program and Elevation’s seribantumab program."

Second Quarter 2022 Financial Results

Merrimack reported a net loss of $478 thousand for the second quarter ended June 30, 2022, or $0.04 per basic and diluted share on a fully diluted basis, compared to a net loss of $759 thousand, or $0.06 per basic and diluted share on a fully diluted basis, for the same period in 2021.

General and administrative expenses for the second quarter ended June 30, 2022, were $486 thousand, compared to $778 thousand for the same period in 2021.

As of June 30, 2022, Merrimack had cash and cash equivalents of $13.4 million, compared to $14.2 million as of December 31, 2021.

As of June 30, 2022, Merrimack had 13.4 million shares of common stock outstanding.

Updates on Programs Underlying Potential Milestone Payments

Ipsen

– On August 3, 2022, Ipsen announced results from its Phase III RESILIENT trial evaluating Onivyde in second-line monotherapy for small cell lung cancer. The announcement indicated that "the primary endpoint OS was not met in patients treated with Onivyde versus topotecan. However, a doubling of the secondary endpoint of objective response rate (ORR) in favor of Onivyde was observed. The safety and tolerability of Onivyde was consistent with its already-known safety profile, and no new safety concerns emerged. The clinical study results will be communicated with the regulatory agency." Ipsen indicated in its update that it will analyze the data further before making decisions about next steps.

– On July 28, 2022, Ipsen provided a public update on its sales performance for the first half of 2022 and indicated that top line data from its continuing Phase 3 study of ONIVYDE in first line pancreatic ductal adenocarcinoma were anticipated to be available during the second half of 2022.

Elevation Oncology

– On May 26, 2022, Elevation Oncology released to the public initial proof-of-concept data from its phase 2 CRESTONE Study evaluating the HER3 monoclonal antibody seribantumab in patients with tumors harboring NRG1 fusions at ASCO (Free ASCO Whitepaper) 2022. The most recent corporate presentation from Elevation indicates that top line data from this trial are expected in 2024.

On August 4, 2022 Galapagos NV (Euronext & NASDAQ: GLPG) reported its first half-year 2022 financial results, a year-to-date business update and its outlook for the remainder of 2022 (Press release, FierceBiotech, AUG 4, 2022, https://www.fiercebiotech.com/biotech/galapagos-sends-another-4-programs-extinction-pivot-car-t-continues [SID1234617693]). The results are further detailed in the H1 2022 financial report available on the financial reports section of the website.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This quarter, we took a first key step in our strategic transformation by entering the field of oncology with the acquisitions of CellPoint and AboundBio. The combined transactions offer the potential for a paradigm shift in CAR-T1 therapy through CellPoint’s breakthrough, decentralized point-of-care supply model, developed in a global strategic collaboration with Lonza, and AboundBio’s cutting-edge fully human antibody-based capabilities to design next-generation CAR-Ts. Patient enrolment in the ongoing Phase 1/2a trials in rrNHL and rrCLL2 is progressing well, and we expect topline results in the first half of next year. Our near-term goal is to bring three additional differentiated, next-generation CAR-T candidates in the clinic over the next three years," said Dr. Paul Stoffels3, CEO and chairman of the board of directors of Galapagos. "We strongly believe that we are taking the right steps in our transformation to accelerate value creation, and we look forward to presenting an in-depth update on our strategy later this year."

"Our Jyseleca franchise is performing very well with robust sales momentum, supported by the regulatory approvals in ulcerative colitis (UC) in Great Britain and Japan earlier this year. The adoption of Jyseleca is strong across Europe with reimbursement for rheumatoid arthritis (RA) in 15 and for UC in 6 countries," added Bart Filius, President, COO and CFO of Galapagos. "Following the acquisitions of CellPoint and AboundBio, we expect that second half operating expenses will increase by approximately €30 million. Therefore, we revised our cash burni guidance of €450-€490 million for the full year 2022 to €480-€520 million. As a result of the strong Jyseleca performance, we increase our full-year net sales guidance of €65-€75 million to €75-€85 million."

Year-to-date operational overview
Commercial & regulatory progress:

Strong adoption across Europe with reimbursement for RA in 15 countries and for UC in 6 countries
Sobi, our distribution and commercialization partner in Eastern and Central Europe, Portugal, Greece, and the Baltic countries, launched Jyseleca in RA in the Czech Republic and Portugal, resulting in €2 million milestone payments to Galapagos in H1
Filed a type II variation for the label update for Jyseleca based on data from the MANTA and MANTA-RAy studies
At the EULAR4 2022 European Congress of Rheumatology, Galapagos hosted several expert sessions and presented 11 abstracts, further establishing us as a key player in RA
Article 20 pharmacovigilance procedure ongoing by the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC), investigating the safety data of all JAK inhibitors for the treatment of certain chronic inflammatory disorders
Pipeline update:

Decided to move forward with GLPG3667 (TYK2 inhibitor) in dermatomyositis with the aim to start a Phase 2 study before year-end
Discontinued development of 4 early-stage programs as part of ongoing scientific and strategic exercise: GLPG3121, a local release formulation JAK1/TYK2 inhibitor with potential in inflammatory diseases; GLPG0555, a JAK1 inhibitor evaluated in osteoarthritis; GLPG4586, a compound with undisclosed mode of action directed toward fibrosis; and GLPG4716, a chitinase inhibitor directed toward idiopathic pulmonary fibrosis
Corporate update:

Entered the field of oncology through the combined acquisitions of CellPoint and AboundBio in all-cash transactions
Received a transparency notification from FMR LLC in Q2 indicating that its shareholding in Galapagos increased and crossed the 5% threshold, to 5.04% of the current outstanding Galapagos shares
Raised €3.6 million through the exercise of subscription rights
Created new subscription rights plans, offering all Galapagos employees the opportunity to participate
All proposed resolutions regarding the extraordinary and annual shareholders’ meetings were adopted by Galapagos’ shareholders on 26 April 2022

H1 2022 financial results
We reported product net sales of Jyseleca in Europe for the first six months of 2022 amounting to €35.4 million (€0.5 million in the first six months of 2021). Our counterparties for the sales of Jyseleca were mainly hospitals and wholesalers located in Belgium, the Netherlands, France, Italy, Spain, Germany, Great Britain, Ireland, Austria, Norway, Sweden and Finland.

Cost of sales related to Jyseleca net sales in the first six months of 2022 amounted to €5.5 million.

Collaboration revenues amounted to €238.6 million for the first six months of 2022, compared to €253.2 million for the first six months of 2021.

Revenues recognized related to the collaboration agreement with Gilead for the filgotinib development were €115.3 million in the first six months of 2022 compared to €136.1 million for the same period last year. This decrease was due to a lower increase in the percentage of completion, partly offset by a higher revenue recognition of milestone payments, strongly influenced by the milestone achieved related to the regulatory approval in Japan for UC in the first half-year of 2022. The revenue recognition related to the exclusive access rights for Gilead to our drug discovery platform amounted to €114.9 million for the first six months of 2022 (€115.7 million for the same period last year).

We have recognized royalty income from Gilead for Jyseleca for €6.3 million in the first six months of 2022 (compared to €1.4 million in the same period last year) of which €3.6 million royalties on milestone income for UC approval in Japan.

Additionally, we recorded milestones of €2.0 million triggered by the first sale of Jyseleca in the Czech Republic and Portugal by our distribution and commercialization partner Sobi, in the first half-year of 2022.

Our deferred income balance on 30 June 2022 includes €1.6 billion allocated to our drug discovery platform that is recognized linearly over the remaining period of our 10-year collaboration, and €0.5 billion allocated to the filgotinib development that is recognized over time until the end of the development period.

Our R&D expenditure in the first six months of 2022 amounted to €249.5 million, compared to €268.8 million for the first six months of 2021. This decrease was primarily explained by a decrease in subcontracting costs from €139.2 million in the first six months of 2021 to €104.1 million in the first six months of 2022, primarily due to the winding down of the ziritaxestat (IPF) program and reduced spend on our Toledo (SIKi) and TYK2 programs. This was partly offset by cost increases for our filgotinib program, on a six month basis compared to the same period in 2021. Personnel costs decreased from €94.2 million in the first half of 2021 to €86.0 million for the same period this year mainly due to a lower number of FTEs as well as lower costs for our subscription right plans. Depreciation and impairment amounted to €32.6 million for the first six months of 2022 (€8.1 million for the same period last year). This increase was primarily due to an impairment of €26.7 million of previously capitalized upfront fees related to our collaboration with Molecure on the dual chitinase inhibitor OATD-01 (GLPG4716). As part of an ongoing strategic exercise to renew and accelerate our portfolio, we decided to return all rights to OATD-01 to Molecure.

Our G&A and S&M expenses amounted to €134.0 million in the first six months of 2022, compared to €105.8 million in the first six months of 2021. This increase was primarily due to the termination of our 50/50 filgotinib co-commercialization cost sharing agreement with Gilead for filgotinib in 2022. The cost increase was also explained by an increase in personnel costs for the first six months of 2022 compared to the same period last year explained by an increase in the commercial work force driven by the commercial launch of filgotinib in Europe.

Other operating income (€17.6 million vs €23.6 million for the same period last year) decreased, mainly driven by lower grant and R&D incentives income.

Net financial income in the first six months of 2022 amounted to €67.7 million, compared to net financial income of €19.9 million for the first six months of 2021. Net financial income in the first six months of 2022 was primarily attributable to €57.4 million of unrealized currency exchange gains on our cash and cash equivalents and current financial investments at amortized cost in U.S. dollars, and to €11.8 million of positive changes in (fair) value of current financial investments. The financial expenses also contained the effect of discounting our long term deferred income of €3.8 million.

We realized a net loss from continuing operations of €32.3 million for the first six months of 2022, compared to a net loss of €77.2 million for the first six months of 2021.

The net profit from discontinued operations for the six months ended 30 June 2021 consisted of the gain on the sale of Fidelta, our fee-for-services business, for €22.2 million.

We reported a group net loss for the first six months of 2022 of €32.3 million, compared to a group net loss of €55.0 million for the first six months of 2021.

Cash position
Current financial investments and cash and cash equivalents totaled €4,429.0 million on 30 June 2022, as compared to €4,703.2 million on 31 December 2021.

Total net decrease in cash and cash equivalents and current financial investments amounted to €274.2 million during the first six months of 2022, compared to a net decrease of €162.7 million during the first six months of 2021. This net decrease was composed of (i) €217.1 million of operational cash burn, (ii) offset by €3.6 million of cash proceeds from capital and share premium increase from exercise of subscription rights in the first six months of 2022, (iii) €11.8 million positive changes in (fair) value of current financial investments and €60.4 million of mainly positive exchange rate differences, and (iv) the cash out from the acquisitions of CellPoint and AboundBio, net of cash acquired, of €132.9 million.

Acquisitions of CellPoint and AboundBio
The preliminary accounting of the acquisitions of CellPoint and AboundBio are included in our H1 2022 condensed consolidated financial statements. To date, we have performed a preliminary fair value analysis of the business combinations. We expect the provisional amount of goodwill to change significantly upon the completion of the purchase price allocation, resulting from the valuation of the different assets and liabilities acquired.

Outlook 2022
Financial guidance:
Following the acquisitions of CellPoint and AboundBio, we revised our cash burn guidance for full year 2022 from €450-€490 million to €480-€520 million. Additionally, we increased our anticipated net sales guidance for Jyseleca from €65-€75 million to between €75 and €85 million.

Expected regulatory events:
We anticipate a Committee for Medicinal Products for Human Use (CHMP) opinion on the type II variation for the Jyseleca label, based on the data from the MANTA and MANTA-RAy studies around year-end. We also expect reimbursement decisions in most key European markets in UC and anticipate that Sobi will further progress with reimbursement discussions in RA and UC in Eastern and Central Europe, Greece, and the Baltic countries. As part of the ongoing article 20 pharmacovigilance procedure on all JAK inhibitors approved in Europe, we expect a CHMP opinion by the end of the year, followed by an adoption by the European Commission shortly afterwards.

Anticipated R&D milestones:
Patient enrolment in the Phase 1/2a trials in rrNHL and rrCLL is progressing well and we anticipate that additional clinical sites will be active by year-end. We are on track to report topline results of both trials in the first half of next year.
We plan to progress TYK2 inhibitor GLPG3667 into a Phase 2 program in dermatomyositis with first patients potentially recruited around year-end.

We continue to explore additional business development opportunities to further leverage our internal capabilities and renew our portfolio, and we look forward to presenting an in-depth update on our corporate strategy later this year.

First half-year 2022 financial report

Galapagos’ financial report for the first six months ended 30 June 2022, including details of the unaudited consolidated results, is accessible on the financial reports section of our website.

Conference call and webcast presentation

Management will host a conference call and webcast presentation followed by Q&A tomorrow 5 August 2022, at 14:00 CET / 8 AM ET. To participate in the conference call, please register in advance using this link. Upon registration, the dial-in numbers will be provided. The conference call can be accessed 10 minutes prior to the start time by using the conference access information provided in the e-mail received at the point of registering, or by selecting the call me feature.

The live webcast can be accessed on the investors section of the Galapagos website, and a replay will be made available shortly after the close of the call.

On August 4, 2022 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported financial results for the second quarter ended June 30, 2022 and provided program updates (Press release, Aeglea BioTherapeutics, AUG 4, 2022, View Source [SID1234617440]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continue to make progress with our Homocystinuria program and are encouraged by the physician and patient interest in advancing our Phase 1/2 trial. There remains a great need for better treatment options for Homocystinuria patients and we look forward to sharing data from this trial later this year," said Anthony Quinn, M.B., Ch.B., Ph. D., president and chief executive officer of Aeglea.

"Given the current state of the financial markets and the implications for Aeglea and the biotechnology industry broadly, we are taking measures to reduce our cash burn and strengthen our financial position," said Jonathan Alspaugh, chief financial officer of Aeglea. "This includes reevaluating the allocation of resources to the pegzilarginase program as all patients have now transitioned to open label studies from which we’ve collected significant data. While we work with the FDA to identify a viable path forward, we will ensure that patients currently on pegzilarginase continue to receive treatment. We have also made the decision to postpone certain activities in our preclinical Cystinuria program due to strategic realignment and manufacturing constraints."

Dr. Quinn continued, "We continue to believe in the power of enzyme engineering to address unmet needs in rare metabolic diseases and that with our platform we have the potential to develop life-changing enzyme therapies for these patients. We remain dedicated to advancing our programs, supporting the patient communities we serve, and building a successful company."

Program and Corporate Updates

AGLE-177 in Homocystinuria

Completed dosing of patients in cohort 2 in Phase 1/2 clinical trial; cohort 3 currently being enrolled.
Opened first U.S. site to support enrollment of clinical trial.
Expect to announce Phase 1/2 clinical data in the fourth quarter of 2022.
Pegzilarginase in Arginase 1 Deficiency

Actively engaged with U.S. Food and Drug Administration (FDA) to discuss items cited in the Refusal to File letter and to identify a viable regulatory approach and path to the resubmission of the Biologics License Application (BLA) for pegzilarginase for the treatment of Arginase 1 Deficiency.
Cystinuria

Continuing certain Investigational New Drug (IND)-enabling activities but have postponed some manufacturing and other activities due to strategic prioritization and limited availability of raw materials.
Corporate

Strengthened the company’s financial position with a registered direct offering resulting in gross proceeds of $45.0 million, which extends the company’s cash runway through the second quarter of 2023.
Second Quarter 2022 Financial Results

As of June 30, 2022, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $90.4 million, including the $45.0 million in gross proceeds from the company’s registered direct offering in May 2022. The company expects its cash, cash equivalents and marketable securities will enable it to fund its operating expenses and capital expenditure requirements through the second quarter of 2023.

Aeglea recognized development fee revenues of $0.6 million in the second quarter of 2022 as a result of its license and supply agreement with Immedica for the commercial rights to pegzilarginase in certain territories outside the U.S. The revenue was related to the PEACE Phase 3 trial and BLA package. In the second quarter of 2021, Aeglea recognized $13.7 million of license and development revenue in connection with the Immedica license and supply agreement.

Research and development expenses totaled $15.4 million for the second quarter of 2022 and $13.6 million for the second quarter of 2021. The increase was primarily associated with expenses related to IND-enabling activities for AGLE-325 for the treatment of Cystinuria and pegzilarginase manufacturing to support ex-U.S. supply. The increase was partially offset by a decrease in expenses related to the PEACE Phase 3 trial of pegzilarginase and reductions in preclinical lab work.

General and administrative expenses totaled $7.7 million for the second quarter of 2022 and $6.8 million for the second quarter of 2021. This increase was primarily due to increased compensation and other personnel expenses as well as commercial capabilities and infrastructure expenses.

Net loss totaled $22.3 million and $6.8 million for the second quarter of 2022 and 2021, respectively, with non-cash stock compensation expense of $2.0 million and $2.1 million for the second quarter of 2022 and 2021, respectively.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality.

The PEACE Phase 3 clinical trial met its primary endpoint with a 76.7% reduction in mean plasma arginine compared to placebo. Additionally, 90.5% of pegzilarginase treated patients achieved normal plasma arginine levels. The arginine lowering was accompanied by a positive trend in Gross Motor Function Measure Part E, a measure of patient mobility. Aeglea’s Phase 1/2 and Phase 2 Open-Label Extension (OLE) data for pegzilarginase in patients with ARG1-D demonstrated clinical improvements and sustained lowering of plasma arginine. Pegzilarginase has received multiple regulatory designations, including Rare Pediatric Disease, Breakthrough Therapy, Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration as well as Orphan Drug Designation from the European Medicines Agency.

About AGLE-177 in Homocystinuria

AGLE-177 is a novel recombinant human enzyme, which is engineered to degrade the amino acid homocysteine and its dimer. AGLE-177 is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of total homocysteine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including thromboembolic vascular events, skeletal abnormalities (including severe osteoporosis), developmental delay, intellectual disability, lens dislocation and severe near sightedness. Preclinical data demonstrated that AGLE-177 improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. AGLE-177 has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease Designation.

On August 4, 2022 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported second quarter financial results for the period ended June 30, 2022 and provided an update on recent company developments (Press release, SpringWorks Therapeutics, AUG 4, 2022, View Source [SID1234617465]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In the second quarter of 2022, we were very pleased to report positive data across each of our core focus areas of rare oncology, BCMA combinations in multiple myeloma, and biomarker-defined metastatic solid tumors, most notably the positive topline data from the Phase 3 DeFi trial as well as encouraging preliminary data from the study evaluating nirogacestat with low-dose belantamab mafodotin in patients with multiple myeloma," said Saqib Islam, Chief Executive Officer of SpringWorks. "The second half of 2022 will be focused on continued preparation for our first potential product launch, including submitting our NDA for nirogacestat in desmoid tumors and progressing the commercial preparations to serve patients with desmoid tumors while continuing to advance our diversified targeted oncology pipeline."

Recent Business Highlights and Upcoming Milestones

Rare Oncology

In May 2022, SpringWorks announced positive topline results from the Phase 3 DeFi trial evaluating nirogacestat in adult patients with progressing desmoid tumors. The DeFi trial met its primary endpoint of improving progression-free survival, or PFS, demonstrating a statistically significant improvement for nirogacestat over placebo, with a 71% reduction in the risk of disease progression (hazard ratio (HR) = 0.29 (95% CI: 0.15, 0.55); p < 0.001). In addition, the trial met all key secondary endpoints, with nirogacestat demonstrating statistically significant improvements as compared to placebo in objective response rate, and patient-reported outcomes. Nirogacestat was generally well tolerated with a manageable safety profile. Additional data are expected to be presented at a medical conference in the second half of 2022 and published in a peer-reviewed journal publication. In addition, SpringWorks plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the second half of 2022, which will be reviewed under the FDA’s Real-Time Oncology Review (RTOR) program.
In June 2022, updated data from the National Cancer Institute, or NCI, sponsored Phase 2 study of nirogacestat in patients with progressing desmoid tumors were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Of the 16 evaluable patients, no disease progression has been observed for any patient while on study. The median time on treatment for all evaluable patients was 4.4 years (range 0.17-7.99 years) with 4/16 patients remaining on treatment over 7 years.
Dosing is ongoing in the Phase 2b ReNeu trial evaluating mirdametinib in adult and pediatric patients with NF1-associated plexiform neurofibromas (NF1-PN). As previously announced, this trial is fully enrolled.
Recruitment is ongoing in a Phase 1/2 clinical trial evaluating mirdametinib in children and young adults with low-grade glioma. Initial data from the first 11 patients treated across two initial dose levels during the Phase 1 dose escalation study were presented at the International Symposium on Pediatric Neuro-Oncology (ISPNO) 2022 meeting.
B-cell Maturation Antigen (BCMA) Combinations in Multiple Myeloma

SpringWorks continues to advance nirogacestat as a potential cornerstone of BCMA combination therapy across modalities in collaboration with eight industry leaders. Five studies are currently ongoing: nirogacestat + GSK’s belantamab mafodotin, nirogacestat + Allogene’s ALLO-715, nirogacestat + Janssen’s teclistamab, nirogacestat + Precision Biosciences’ PBCAR269A, and nirogacestat + Pfizer’s elranatamab; three additional studies are planned: nirogacestat + Seagen’s SEA-BCMA, nirogacestat + AbbVie’s ABBV-383, and nirogacestat + Regeneron’s REGN5458.
In June 2022, initial clinical data from the GSK-sponsored Phase 1/2 study evaluating nirogacestat in combination with low-dose belantamab mafodotin in patients with relapsed or refractory multiple myeloma were presented at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting. At the time of data cut-off, the objective response rate at low-dose (0.95 mg/kg) belantamab mafodotin plus nirogacestat across the dose escalation, or DE, and cohort expansion, or CE, arms was 38% in 24 patients, with 17% of patients achieving a very good partial response or better. An encouraging safety profile for the combination was observed, with Grade 3 ocular adverse events occurring in 1/14 (7%) patients in the CE cohort with the low-dose belantamab mafodotin plus nirogacestat combination compared to 7/14 patients (50%) in the belantamab mafodotin monotherapy arm, using the Keratopathy Visual Acuity, or KVA, ocular toxicity grading scale. The DE cohort utilized the CTCAE-5 ocular toxicity grading scale; the low-dose belantamab mafodotin plus nirogacestat combination demonstrated Grade 3 ocular adverse events in 2/10 (20%) patients. SpringWorks expects the next data cut from the randomized Phase 2 cohort expansion study to occur towards the end of 2022. In addition, new sub-studies will evaluate low-dose belantamab mafodotin and nirogacestat with lenalidomide/dexamethasone and pomalidomide/dexamethasone to support potential development in earlier lines of therapy.
In July 2022, SpringWorks entered into a co-supported collaborative study agreement with GSK and the Hellenic Society of Haematology to conduct a Phase 1/2 study to evaluate low-dose belantamab mafodotin and nirogacestat in combination with lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma patients. Evangelos Terpos, MD, PhD, Professor of Hematology in the Department of Clinical Therapeutics of the National & Kapodistrian University of Athens, School of Medicine, Athens, Greece will serve as the principal investigator of the study.
Biomarker-Defined Metastatic Solid Tumors

Initial clinical data from the BeiGene-sponsored Phase 1b/2 trial evaluating mirdametinib with BeiGene’s RAF dimer inhibitor, lifirafenib, in adult patients with RAS/RAF mutant and other MAPK pathway aberrant solid tumors were presented at a SpringWorks-sponsored R&D Day in June 2022. Clinical responses were observed across a range of MAPK-altered tumors during the dose escalation portion of the study and there was evidence of acceptable safety and tolerability with multiple patients exposed to the combination for more than two years. SpringWorks expects these data to be presented at a medical conference in the second half of 2022.
Initial clinical data from a Phase 1 trial evaluating BGB-3245, a selective RAF dimer inhibitor being developed by MapKure, LLC, a joint venture between SpringWorks and BeiGene, in adult patients with RAF mutant solid tumors were presented at a SpringWorks-sponsored R&D Day in June 2022. Objective responses were seen in patients with BRAF, KRAS, and NRAS mutations, including in some patients who had exhausted standard of care therapeutic options, and the emerging safety profile of BGB-3245 is consistent with other MAPK pathway inhibitors. SpringWorks expects these data to be presented at a medical conference in the second half of 2022. BGB-3245 monotherapy is advancing into cohort expansion studies and SpringWorks expects to initiate a combination study of BGB-3245 and mirdametinib in the second half of 2022. To support the further advancement of BGB-3245, an additional equity financing in MapKure was completed in June 2022, which included participation from SpringWorks and BeiGene.
In July 2022, SpringWorks entered into a Cooperative Research and Development Agreement (CRADA) with the NCI Cancer Therapy Evaluation Program (CTEP) to collaborate on the non-clinical and clinical development of mirdametinib.
General Corporate

In July 2022, SpringWorks appointed Carlos Albán to its Board of Directors. Mr. Albán previously served as Vice Chairman and Chief Commercial Officer at AbbVie until his retirement last year and brings over 30 years of experience in global commercial strategy and operations.
Second Quarter 2022 Financial Results

Research and Development (R&D) Expenses: R&D expenses were $38.0 million for the second quarter, compared to $32.1 million for the comparable period of 2021. The increase in R&D expense was primarily attributable to an increase in internal costs driven by the growth in employee costs associated with increases in the number of personnel, including an increase in stock-based compensation expense, and an increase in external costs related to drug manufacturing, clinical trial and other research, partially offset by a decrease in licensing costs related to the nonrefundable upfront payment to KU Leuven and VIB for the in-licensing of the TEAD inhibitor program in May 2021.
General and Administrative (G&A) Expenses: G&A expenses were $31.0 million for the second quarter, compared to $14.9 million for the comparable period of 2021. The increase in G&A expense was primarily attributable to an increase in internal costs driven by the growth in employee costs associated with increases in the number of personnel, including an increase in stock-based compensation expense as we continue to expand our operations to support the organization, and an increase in information technology costs and consulting and professional services, including legal, regulatory and compliance, as we continue to build new capabilities, including commercial.
Net Loss Attributable to Common Stockholders: SpringWorks reported net loss of $69.1 million, or $1.41 per share, for the second quarter of 2022. This compares to a net loss of $47.0 million, or $0.97 per share, for the comparable period of 2021.
Cash Position: Cash, cash equivalents and marketable securities were $334.5 million as of June 30, 2022.
COVID-19 Update

To date, the COVID-19 pandemic has had a relatively modest impact on SpringWorks’ business operations, in particular on SpringWorks’ clinical trial programs, and SpringWorks is undertaking considerable efforts to mitigate the various challenges presented by this crisis. For further details and descriptions of the risks associated with the COVID-19 pandemic, please see the Risk Factors in SpringWorks’ periodic filings with the Securities and Exchange Commission, or SEC, and refer to the Forward-Looking Statements section in this press release.