Agios Pharmaceuticals has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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On May 5, 2022 IntelGenx Technologies Corp. (TSX:IGX) (OTCQB:IGXT) ("IntelGenx"), a leader in pharmaceutical films, reported that it will release its first quarter 2022 financial results after market close on Thursday, May 12, 2022 (Press release, IntelGenx, MAY 5, 2022, View Source [SID1234613800]).

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An accompanying conference call will be hosted by Dr. Horst G. Zerbe, Chief Executive Officer, and Mr. Andre Godin, President and Chief Financial Officer, to discuss the results and provide a business update. Details of the conference call and webcast are below:

The call will also be broadcast live and archived on the Company’s website at www.intelgenx.com under "Webcasts" in the Investors section.

On May 5, 2022 Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, reported financial results for the first quarter 2022 (Press release, Prothena, MAY 5, 2022, View Source [SID1234613796]).

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"We are excited to kick off 2022 with a strong first quarter, further reinforcing continued execution across our portfolio. We remain focused on the Phase 3 AFFIRM-AL trial of birtamimab being conducted under a SPA agreement with FDA. We also achieved multiple milestones in our PRX012 program, our next-generation, subcutaneous anti-amyloid beta antibody, having received FDA clearance of the IND, initiated a Phase 1 clinical study and received Fast Track designation from FDA. Additionally, we presented positive preclinical findings for our Alzheimer’s and Parkinson’s active vaccine candidates at AD/PD 2022, further highlighting the depth of our neurodegenerative pipeline," said Gene Kinney, Ph.D., President and Chief Executive Officer of Prothena. "Later this year, we look forward to clinical data from our PRX005 Phase 1 study and the initiation of a Phase 1 multiple ascending dose study for PRX012. We will continue to drive meaningful growth this year across our portfolio and our strong capital position supports our leadership in protein dysregulation."

First Quarter and Recent Business Highlights and Upcoming Milestones

Neurodegenerative Diseases Portfolio

Alzheimer’s Disease (AD)

PRX012, a potential best-in-class treatment for AD, is an investigational monoclonal antibody targeting a key epitope at the N-terminus of amyloid beta (Aβ) with high binding potency supporting subcutaneous administration

Received U.S. Food and Drug Administration (FDA) clearance of the Investigational New Drug (IND) application
Received Fast Track designation for PRX012 from FDA for the treatment of AD
Initiated Phase 1 single ascending dose (SAD) study, a randomized, double-blind, placebo-controlled study to evaluate safety, tolerability, immunogenicity, and pharmacokinetics in healthy volunteers and patients with Alzheimer’s disease
Phase 1 multiple ascending dose (MAD) study initiation expected by year-end 2022
Topline Phase 1 data expected in 2023
PRX005, a potential best-in-class treatment for AD, is an investigational antibody that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, a protein implicated in diseases including AD, frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), chronic traumatic encephalopathy (CTE), and other tauopathies. PRX005 is part of the global neuroscience research and development collaboration with Bristol Myers Squibb

Topline Phase 1 data expected in 2022
Dual Aβ /tau vaccine, a potential first-in-class treatment and prevention therapy for AD, is a dual-target vaccine targeting key epitopes within the Aβ and tau proteins to promote amyloid clearance and blockade of pathogenic tau

Oral presentation on preclinical data at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2022) in March demonstrating that Prothena’s dual Aβ/tau vaccine generated anti-Aβ and anti-tau antibodies to enable phagocytosis of Aβ and to neutralize tau
IND filing expected in 2023
Parkinson’s Disease (PD)

Prasinezumab, a potential first-in-class treatment for PD, is a humanized monoclonal antibody designed to target key epitopes within the C-terminus of alpha-synuclein and is the focus of the worldwide collaboration with Roche

Oral presentation by partner Roche at AD/PD 2022 on the Phase 2 PASADENA study of prasinezumab, further supports a potential effect on delaying motor progression in patients
Phase 2b PADOVA study results expected in 2024
Rare Peripheral Amyloid Diseases Portfolio

AL Amyloidosis

Birtamimab, a potential best-in-class amyloid depleter treatment for AL amyloidosis, is an investigational humanized monoclonal antibody designed to directly neutralize soluble toxic aggregates and promote clearance of amyloid that causes organ dysfunction and failure

Confirmatory Phase 3 AFFIRM-AL study results expected in 2024
ATTR Amyloidosis

PRX004, a potential first-in-class treatment for ATTR amyloidosis, is a humanized monoclonal antibody designed to deplete the pathogenic, non-native forms of the TTR protein, that is being developed by Novo Nordisk for the treatment of ATTR cardiomyopathy

Novo Nordisk expects to initiate a Phase 2 study of PRX004 for the treatment of ATTR cardiomyopathy in 2Q 2022
Upcoming Investor Conferences

Members of the senior management team will present and participate in investor meetings at the following upcoming investor conferences:

BofA Securities 2022 Healthcare Conference, May 10, 2022, at 9:20 AM PT/12:20 PM ET
H.C. Wainwright Global Investment Conference, May 24, 2022, on demand presentations available starting at 7:00 AM ET
First Quarter 2022 Financial Results

For the first quarter of 2022, Prothena reported a net loss of $36.3 million, as compared to a net loss of $36.7 million for the first quarter of 2021. Net loss per share for the first quarter of 2022 was $0.78, as compared to net loss per share of $0.91 for the first quarter of 2021.

Prothena reported total revenue of $1.2 million for the first quarter of 2022, primarily from collaboration revenue from Bristol Myers Squibb. As compared to total revenue of $0.2 million for the first quarter of 2021, from collaboration and license revenue from Roche.

Research and development (R&D) expenses totaled $27.3 million for the first quarter of 2022, as compared to $21.1 million for the first quarter of 2021. The increase in R&D expense for the first quarter of 2022 compared to the same period in the prior year was primarily due to higher manufacturing costs, primarily related to the birtamimab program, higher personnel related expenses, higher clinical trial expenses primarily related to the PRX012, birtamimab and PRX005 programs, and higher other R&D expense, offset in part by lower collaboration expenses related to the prasinezumab program with Roche as a result of the cost share opt-out exercised in May 2021. R&D expenses included non-cash share-based compensation expense of $3.3 million for the first quarter of 2022, as compared to $2.0 million for the first quarter of 2021.

General and administrative (G&A) expenses totaled $11.8 million for the first quarter of 2022, as compared to $11.1 million for the first quarter of 2021. The increase in G&A expenses for the first quarter of 2022 compared to the same period in the prior year was primarily related to higher personnel expense and higher consulting expenses, offset in part by lower legal expense and lower expense for our director and officer insurance premium. G&A expenses included non-cash share-based compensation expense of $4.3 million for the first quarter of 2022, as compared to $4.2 million for the first quarter of 2021.
Total non-cash share-based compensation expense was $7.7 million for the first quarter of 2022, as compared to $6.2 million for the first quarter of 2021.

As of March 31, 2022, Prothena had $544.3 million in cash, cash equivalents and restricted cash, and no debt.

As of April 28, 2022, Prothena had approximately 46.8 million ordinary shares outstanding.

2022 Financial Guidance

The Company continues to expect the full year 2022 net cash used in operating and investing activities to be $120 to $132 million, which includes an expected $40 million clinical milestone payment from Novo Nordisk and expects to end the year with approximately $454 million in cash, cash equivalents and restricted cash (midpoint). The estimated full year 2022 net cash used in operating and investing activities is primarily driven by an estimated net loss of $154 to $170 million, which includes an estimated $32 million of non-cash share-based compensation expense. (Press release, Prothena, MAY 5, 2022, View Source [SID1234613796])

On May 5, 2022 ChemoCentryx, Inc., (Nasdaq: CCXI), reported financial results for the first quarter ended March 31, 2022 and provided an overview of recent corporate highlights (Press release, ChemoCentryx, MAY 5, 2022, View Source [SID1234613795]).

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"Strong performance was evident in the first quarter," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "The traction to-date is clear: all key performance indicators are up and Q1 revenue exceeded our model. A five-fold increase in net sales occurred versus Q4 2021; there was a nearly three-fold increase in unique prescribers, and a greater than three-fold increase of patients on drug this quarter. Further, referrals are coming from a growing number of first time as well as repeat prescribers. In my view, all of this shows that we are executing on plan – and we believe this is just the start for TAVNEOS.

Beyond TAVNEOS, compelling data now is emerging from the Phase I study of our orally administered PD-L1 immune checkpoint inhibitor, CCX559. The PK and PD data presented at the recent American Association of Cancer Research meeting show that CCX559 dosed once daily is pharmacologically active in cancer patients, and the data support the fact that 120 mg once a day is therapeutically relevant. We are on track to advance into the next phase of clinical development in the second half of 2022. A very promising start to the year in my view, one that shows both patients and shareholders alike that CCXI is fiercely dedicated to the proposition of improving lives and creating value."

Key First Quarter 2022 Highlights and Recent Developments

TAVNEOS (avacopan) Commercial Progress
Commercial Execution: TAVNEOS generated net product sales of approximately $5.4 million during the first quarter of 2022 from US commercial sales.
248 new patient start forms (PSFs) received for TAVNEOS during the first quarter of 2022.
281 unique prescribers to date.
277 patients on drug (POD) as of March 31, 2022.
Continued Traction Ex-US: TAVNEOS was approved in the European Union (EU) in January 2022, followed by an additional approval in Canada in April 2022 for the treatment of ANCA-associated vasculitis.
ChemoCentryx’s partner, Vifor Pharma, recently initiated marketing activities for TAVNEOS in Germany during February followed by Austria in March, and expects to launch in other markets in 2022. Vifor will pay ChemoCentryx royalties in the teens to the mid-20s percent on aggregate net sales from the Vifor territories outside the US.
The EU approval triggered a non-refundable $45 million milestone payment from Vifor. The cash payment has been received in full and is included in the Company’s reported cash balance. Collaboration revenue (distinct from product sales) will be recognized in the future as underlying development activities occur, in accordance with ASC606, which is currently estimated to be over a four year period, subject to adjustment from time to time.
TAVNEOS (avacopan) Clinical Development:
Lupus nephritis (LN): ChemoCentryx expects to receive feedback from the FDA mid-year 2022 regarding the clinical development plan for TAVNEOS in LN, which it plans to initiate during the second half of 2022.
Severe hidradenitis suppurativa (HS): The Company plans to meet with the FDA to discuss the Phase III development of TAVNEOS in patients with Hurley Stage III (severe) HS late in the second quarter, with the goal of initiating a Phase III clinical trial in those patients in the second half of 2022.
C3 glomerulopathy (C3G): The Company anticipates meeting with the FDA during the second half of the year to discuss the dataset from the ACCOLADE Phase II clinical trial of TAVNEOS in the very rare disorder of C3G, for which there are no FDA approved therapies.
CCX559 Clinical Development:
CCX559 is a novel, orally administered PD-L1 checkpoint inhibitor being developed for the treatment of various cancers, currently being evaluated in a Phase I dose escalation study. An orally administered small molecule inhibitor of PD-L1 could have advantageous properties compared to approved monoclonal antibodies, such as better penetration into solid tumors, reduced immunogenicity, lack of Fc-mediated side effects and convenience of oral administration.
At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 in April, ChemoCentryx reported preclinical data along with pharmacokinetic (PK) and pharmacodynamic (PD) data available from patients with advanced cancer who were enrolled in the first three dose cohorts of the ongoing Phase I study. Data show CCX559 is pharmacologically active in cancer patients and exhibits immune system activating properties.
ChemoCentryx intends to present additional clinical data, including further escalating dose level data, at major oncology conferences through 2022. The Company is on track to initiate a Phase Ib/II clinical trial to measure anti-tumor effects of CCX559 more directly during the second half of 2022.
Cash Position: The Company maintained a strong balance sheet with cash, cash equivalents and investments of approximately $371.8 million as of March 31, 2022. This includes a $45 million milestone received from Vifor Pharma in the first quarter of 2022 following the EU approval of TAVNEOS.
First Quarter 2022 Financial Results

TAVNEOS US net product sales were $5.4 million for the first quarter ended March 31, 2022. Collaboration and license revenue was $0.1 million for the quarter ended March 31, 2022, compared to $10.2 million in 2021. The decrease in collaboration revenue was attributable to the $10.0 million milestone received in 2021 for the acceptance of the Japanese NDA, for TAVNEOS in the treatment of ANCA-associated vasculitis.

Collaboration revenue is recognized ratably in proportion to actual costs incurred as a percentage of total program budgeted costs as the Company completes its performance obligations under its alliance agreements. The $45.0 million non-refundable regulatory milestone received upon TAVNEOS approval in Europe during the first quarter of 2022 is currently estimated to be recognized over a four year period, subject to adjustment from time to time.

Cost of sales for the first quarter ended March 31, 2022, was $0.2 million. Costs incurred for manufacturing campaigns initiated prior to the October 2021 FDA approval of TAVNEOS were recorded as research and development expense. Accordingly, cost of sales in the near term will likely be lower than in later periods given the sales of pre-approval inventory will carry little to no manufacturing costs since such costs were previously expensed to research and development expense.

Research and development expenses were $17.5 million for the first quarter of 2022, compared to $23.4 million for the same period in 2021. Based on the accounting treatment of pre-approval manufacturing campaigns described above, the decrease was primarily attributable to manufacturing costs of commercial drug supply in the first quarter of 2021. In addition, the completion of the TAVNEOS AURORA Phase IIb clinical trial in patients with HS in 2021 contributed to lower Phase II related expenses. These decreases were partially offset by higher research and drug discovery expenses, including those associated with the development of CCX559, our orally available small molecule checkpoint (PD-L1/PD-1) inhibitor.

Selling, general and administrative expenses were $26.0 million for the first quarter of 2022, compared to $16.3 million for the same period in 2021. The increase was primarily attributable to higher employee-related expenses and professional fees, including those associated with the Company’s launch and commercialization of TAVNEOS.

Net loss for the first quarter of 2022 was $38.6 million, compared to net loss of $29.7 million for the same period in 2021.

Total shares outstanding as of March 31, 2022, were approximately 71.1 million shares.

Cash, cash equivalents and investments totaled approximately $371.8 million as of March 31, 2022.

Conference Call and Webcast

The Company will host a conference call and webcast today, May 5, 2022, at 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time. To participate by telephone, please dial (877) 303-8028 (Domestic) or (760) 536-5167 (International). The conference ID number is 6597218. A live and archived audio webcast can be accessed through the Investors section of the Company’s website at www.ChemoCentryx.com. The archived webcast will remain available on the Company’s website for fourteen (14) days following the call.

INDICATION

TAVNEOS (avacopan) is indicated as an adjunctive treatment of adult patients with severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]) in combination with standard therapy including glucocorticoids. TAVNEOS does not eliminate glucocorticoid use.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
Serious hypersensitivity to avacopan or to any of the excipients

WARNINGS AND PRECAUTIONS
Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking TAVNEOS, including life-threatening events. Obtain liver test panel before initiating TAVNEOS, every 4 weeks after start of therapy for six months and as clinically indicated thereafter. Monitor patients closely for hepatic adverse reactions and consider pausing or discontinuing treatment as clinically indicated (refer to section 5.1 of the Prescribing Information). TAVNEOS is not recommended for patients with active, untreated and/or uncontrolled chronic liver disease (e.g., chronic active hepatitis B, untreated hepatitis C, uncontrolled autoimmune hepatitis) and cirrhosis. Consider the risk and benefit before administering this drug to a patient with liver disease.

Serious Hypersensitivity Reactions: Cases of angioedema occurred in a clinical trial, including one serious event requiring hospitalization. Discontinue immediately if angioedema occurs and manage accordingly. TAVNEOS must not be re-administered unless another cause has been established.

Hepatitis B Virus (HBV) Reactivation: Hepatitis B reactivation, including life threatening hepatitis B, was observed in the clinical program. Screen patients for HBV. For patients with evidence of prior infection, consult with physicians with expertise in HBV and monitor during TAVNEOS therapy and for six months following. If patients develop HBV reactivation, immediately discontinue TAVNEOS and concomitant therapies associated with HBV reactivation and consult with experts before resuming.

Serious Infections: Serious infections, including fatal infections, have been reported in patients receiving TAVNEOS. The most common serious infections reported in TAVNEOS group were pneumonia and urinary tract infections. Avoid use of TAVNEOS in patients with active, serious infection, including localized infections. Consider the risks and benefits before initiating TAVNEOS in patients with chronic infection, at increased risk of infection or who have been to places where certain infections are common.

ADVERSE REACTIONS
The most common adverse reactions (≥5% of patients and higher in the TAVNEOS group vs. prednisone group) were: nausea, headache, hypertension, diarrhea, vomiting, rash, fatigue, upper abdominal pain, dizziness, blood creatinine increased and paresthesia.

DRUG INTERACTIONS
Avoid coadministration of TAVNEOS with strong and moderate CYP3A4 enzyme inducers. Reduce TAVNEOS dose when co-administered with strong CYP3A4 enzyme inhibitors to 30 mg once daily. Monitor for adverse reactions and consider dose reduction of certain sensitive CYP3A4 substrates.

Please see Full Prescribing Information and Medication Guide for TAVNEOS.

About TAVNEOS (avacopan)

TAVNEOS (avacopan), approved by the FDA as an adjunctive treatment of ANCA-associated vasculitis, is a first-in-class, orally administered small molecule that employs a novel, highly targeted mode of action in complement-driven autoimmune and inflammatory diseases. While the precise mechanism in ANCA vasculitis has not been definitively established, TAVNEOS, by blocking the complement 5a receptor (C5aR) for the pro-inflammatory complement system fragment known as C5a on destructive inflammatory cells such as blood neutrophils, is presumed to arrest the ability of those cells to do damage in response to C5a activation, which is known to be the driver of ANCA vasculitis. TAVNEOS’s selective inhibition of only the C5aR is believed to leave the beneficial C5a pathway through the C5L2 receptor functioning normally.

ChemoCentryx is also developing TAVNEOS for the treatment of patients with C3 glomerulopathy (C3G), severe hidradenitis suppurativa (HS) and Lupus Nephritis (LN). The US Food and Drug Administration granted TAVNEOS orphan drug designation for ANCA-associated vasculitis and C3G. The European Commission has granted orphan medicinal product designation for TAVNEOS for the treatment of two forms of ANCA-associated vasculitis: microscopic polyangiitis and granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis), as well as for C3G. TAVNEOS has not been approved for indications discussed as in development, and the safety and efficacy of those uses has not been established.

About ANCA-Associated Vasculitis

ANCA-associated vasculitis is a systemic disease in which over-activation of the complement pathway further activates neutrophils, leading to inflammation and destruction of small blood vessels. This results in organ damage and failure, with the kidney as the major target, and is fatal if not treated. Currently, treatment for ANCA-associated vasculitis consists of courses of non-specific immuno-suppressants (cyclophosphamide or rituximab), combined with the administration of daily glucocorticoids (steroids) for prolonged periods of time, which can be associated with significant clinical risk including death from infection.

On May 5, 2022 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported consolidated financial results for the first quarter ended March 31, 2022 and reiterated full year 2022 product revenue guidance (Press release, Vertex Pharmaceuticals, MAY 5, 2022, View Source [SID1234613793]).

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"Following upon our success in transforming the treatment of cystic fibrosis, Vertex’s unique and differentiated R&D strategy continues to deliver with positive Phase 2 proof-of-concept studies in multiple disease areas, and another wave of therapies set to enter the clinic in the second half of this year," said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex. "With yet another quarter of strong revenue performance characterized by 22% year-over-year growth, we are well positioned for continued innovation and sustained growth as we work to bring additional transformative medicines to more patients around the globe."

Starting in the first quarter of 2022, Vertex no longer excludes research and development charges resulting from upfront or contingent milestone payments in connection with collaborations, asset acquisitions and/or licensing of third-party intellectual property rights from its Non-GAAP financial measures. Non-GAAP financial measures for the first quarter of 2021 have been recast to reflect this change.

Product revenues increased 22% to $2.10 billion compared to the first quarter of 2021, primarily driven by the strong launches of TRIKAFTA/KAFTRIO in multiple countries internationally and the strong performance of TRIKAFTA in the U.S., including the June 2021 launch of TRIKAFTA in children 6-11 years old in the U.S. Net product revenues in the first quarter of 2022 increased 9% to $1.37 billion in the U.S. and increased 55% to $729 million outside the U.S., compared to the first quarter of 2021.

GAAP and Non-GAAP net income increased compared to the first quarter of 2021, driven by strong product revenue growth.

Cash, cash equivalents and marketable securities as of March 31, 2022 were $8.2 billion, an increase of approximately $0.7 billion compared to December 31, 2021. The increase was primarily driven by strong revenue growth and operating cash flow.

Starting in the first quarter of 2022, Vertex no longer excludes research and development charges resulting from upfront or contingent milestone payments in connection with collaborations, asset acquisitions and/or licensing of third-party intellectual property rights from its Non-GAAP financial measures.

Key Business Highlights

Cystic Fibrosis (CF) Marketed Products

Vertex anticipates the number of CF patients treated with our medicines will continue to grow as the uptake of TRIKAFTA in the U.S. and the launches of KAFTRIO outside the U.S. continue, and as we enter into additional reimbursement agreements and achieve new approvals for the treatment of younger patients. Recent progress includes:

Health Canada granted marketing authorization for TRIKAFTA in children 6 to 11 years of age. With this approval, approximately 500 children with CF are newly eligible for treatment with a CFTR modulator.
Vertex signed a reimbursement agreement with the Australian Pharmaceutical Benefits Scheme for TRIKAFTA (ivacaftor/tezacaftor/elexacaftor) for the treatment of patients with cystic fibrosis 12 years and older with at least one F508del mutation in the CF transmembrane conductance regulator (CFTR) gene. With this agreement, approximately 700 people in Australia will have access to a CFTR modulator therapy for the first time.
Vertex completed enrollment in the Phase 3 study of TRIKAFTA/KAFTRIO in children 2 to 5 years old. The Company anticipates filing a supplementary new drug application (sNDA) with the FDA before the end of 2022.
In March, Vertex filed an sNDA with the FDA for ORKAMBI for the use of ORKAMBI in children 12 months to less than 24 months old. Vertex intends to submit regulatory filings in Europe in Q2 2022.
In January, the European Commission and the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) approved a label extension for KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in a combination regimen with ivacaftor, for the treatment of CF in children ages 6 through 11 years old who have at least one F508del mutation in the CF transmembrane conductance regulator (CFTR) gene. With these approvals, approximately 1,900 children are newly eligible for KAFTRIO.
In 2021, Vertex presented the first long-term follow-up data for TRIKAFTA, demonstrating no loss in mean lung function at 96 weeks, a first for any CFTR modulator to date in people with F/F and F/MF mutations. Vertex has now completed a comparison of long-term data in TRIKAFTA patients to matched untreated controls, and will present these data at an upcoming medical congress.
TRIKAFTA/KAFTRIO is now approved and reimbursed or accessible in more than 25 countries.

R&D pipeline

Vertex is delivering on a diversified pipeline of potentially transformative small molecule, cell and genetic therapies aimed at serious diseases. Recent and anticipated progress for key pipeline programs is summarized below.

Cystic Fibrosis

Vertex continues to pursue next-in-class, small molecule CFTR modulator therapies as well as new treatment options for the approximately 5,000 patients who cannot benefit from CFTR modulators alone.

Vertex is conducting two Phase 3 global, randomized, double-blind, active-controlled clinical trials (SKYLINE 102 and SKYLINE 103) evaluating Vertex’s new once-daily investigational triple combination of VX-121/tezacaftor/VX-561 in patients with CF. The SKYLINE 102 and SKYLINE 103 trials will compare the efficacy and safety of VX-121/tezacaftor/VX-561 to TRIKAFTA. More than 180 sites across both studies are open and enrolling, and enrollment in both trials is expected to be completed in late 2022 or early 2023.
In collaboration with Moderna, Vertex is developing CF mRNA therapeutics designed to treat the underlying cause of CF by programming cells in the lungs to produce functional CFTR protein for the treatment of the approximately 5,000 people with CF who do not produce any CFTR protein. IND-enabling studies have been completed, and Vertex is on track to submit an IND for this program in 2H 2022.
Beta Thalassemia and Sickle Cell Disease (SCD)

The CTX001 program employs a non-viral ex vivo CRISPR gene-editing therapy, which is being developed as a potential functional cure for transfusion-dependent thalassemia (TDT) and severe sickle cell disease (SCD). Vertex is developing CTX001 in collaboration with CRISPR Therapeutics.

Enrollment is complete in the ongoing Phase 3 clinical trials in TDT and SCD, with more than 75 patients dosed to date. Vertex anticipates presenting updated data from the clinical trials, with more patients and longer follow-up, at medical conferences in 2022.
Two new Phase 3 studies of CTX001 were initiated in pediatric patients with TDT and SCD.
Vertex plans to submit global regulatory filings for CTX001 in TDT and SCD in late 2022.
APOL1-Mediated Kidney Disease (AMKD)

Vertex has discovered multiple oral, small molecule inhibitors of APOL1 function, pioneering a new class of medicines that target an underlying genetic driver of kidney disease.

In March, Vertex initiated pivotal development of VX-147 in a single Phase 2/3 study in patients with AMKD with two APOL1 mutations and proteinuric kidney disease.
This Phase 2/3 adaptive study will first evaluate two doses of VX-147 to select a dose for Phase 3 and subsequently evaluate the efficacy and safety of the single, selected dose in the Phase 3 portion of the study. The primary efficacy endpoint for the final analysis is eGFR slope in patients receiving the VX-147 selected dose compared to placebo at two years. The study is designed to have a pre-planned interim analysis at Week 48 evaluating eGFR slope, supported by a percent change from baseline in proteinuria in the VX-147 arm versus placebo. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval of VX-147 in the U.S. for patients with AMKD.
Pain (NaV1.8)

Vertex has discovered multiple selective small molecule inhibitors of NaV1.8 with the objective of creating a new class of pain medicines that have the potential to provide effective pain relief, without the limitations of opioids.

In March, Vertex reported positive data from two Phase 2 dose ranging acute pain studies with VX-548, one following bunionectomy surgery and the other following abdominoplasty surgery. Both studies met their primary endpoint and established proof of concept for VX-548.
Vertex plans to advance VX-548 into pivotal development in acute pain in the second half of 2022, following discussions with regulators.
Type 1 Diabetes (T1D)

Vertex is evaluating cell therapies using stem cell-derived islets to replace the endogenous insulin-producing islet cells that are destroyed in people with T1D with the goal of developing a potential functional cure for this disease.

VX-880 is a stem cell-derived, fully differentiated islet replacement therapy, used in combination with standard immunosuppression to protect the implanted cells. VX-880 is being evaluated in a Phase 1/2 clinical trial for the treatment of T1D.
This program has been placed on clinical hold in the U.S. by the FDA, based on their determination of insufficient information for dose escalation with the product. Vertex is working collaboratively and with urgency to understand and address the FDA’s questions.
Vertex previously announced:
The first patient, who received a half dose of VX-880, is insulin-independent with an HbA1C of 5.2% at Day 270.
The second patient, who also received a half dose of VX-880, demonstrated restoration of glucose-responsive insulin production and significant improvement in glycemic control with reductions in exogenous insulin requirements.
Taken together, results in the first two patients establish proof-of-concept for VX-880 in the treatment of T1D. Per protocol, the Independent Data Monitoring Committee reviewed the totality of the safety data from the first two patients dosed and recommended advancement to Part B of the study, and treatment with the full target dose.
The third patient treated with VX-880 received the full target dose and has reached the Day 29 follow-up milestone.
Across the program, VX-880 has been generally well tolerated to date. There have been no serious adverse events (SAEs) considered related to VX-880. The majority of adverse events (AEs) were mild or moderate in all patients treated to date. The safety profile was generally consistent with the immunosuppressive regimen used in the study and the perioperative period.
Vertex is continuing to advance additional programs in T1D, in which these same stem cell-derived islets are encapsulated and implanted in an immunoprotective device or modified to produce hypoimmune stem cell islets with the goal of eliminating the need for immunosuppression.
Vertex is on track to submit an IND for the cells plus device program in 2022.
Vertex expects to share additional data for VX-880 at medical conferences this year.

Alpha-1 Antitrypsin (AAT) Deficiency

Vertex is working to address the underlying genetic cause of alpha-1 antitrypsin (AAT) deficiency by developing novel small molecule correctors of Z-AAT protein folding, with a goal of increasing the secretion of functional AAT into the blood and addressing both the lung and the liver aspects of AAT deficiency.

Vertex is on track to advance one or more novel small molecule Z-AAT correctors into the clinic in 2022.
Duchenne Muscular Dystrophy (DMD)

Vertex is investigating a novel approach to treating DMD by delivering CRISPR/Cas9 gene-editing technology to muscle cells with the goal of restoring near-full length dystrophin protein expression by targeting specific mutations in the dystrophin gene that cause the disease.

Vertex has advanced its first in vivo gene editing therapy for DMD into IND-enabling studies.
Consistent with its overall strategy, Vertex takes a portfolio approach to all of its programs, with additional assets in CF, SCD, Beta Thalassemia, AMKD, T1D, Pain, and AATD in earlier stages of development.

Non-GAAP Financial Measures

In this press release, Vertex’s financial results and financial guidance are provided in accordance with accounting principles generally accepted in the United States (GAAP) and using certain non-GAAP financial measures. In particular, non-GAAP financial results and guidance exclude from Vertex’s pre-tax income (i) stock-based compensation expense, (ii) gains or losses related to the fair value of the company’s strategic investments, (iii) increases or decreases in the fair value of contingent consideration, (iv) acquisition-related costs and (v) other adjustments. The company’s non-GAAP financial results also exclude from its provision for income taxes the estimated tax impact related to its non-GAAP adjustments to pre-tax income described above and certain discrete items. These results should not be viewed as a substitute for the company’s GAAP results and are provided as a complement to results provided in accordance with GAAP. Management believes these non-GAAP financial measures help indicate underlying trends in the company’s business, are important in comparing current results with prior period results and provide additional information regarding the company’s financial position that the company believes is helpful to an understanding of its ongoing business. Management also uses these non-GAAP financial measures to establish budgets and operational goals that are communicated internally and externally, to manage the company’s business and to evaluate its performance. The company’s calculation of non-GAAP financial measures likely differs from the calculations used by other companies. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the attached financial information.

The company provides guidance regarding combined R&D and SG&A expenses and effective tax rate on a non-GAAP basis. The guidance regarding combined GAAP and non-GAAP R&D and SG&A expenses does not include estimates associated with any potential future business development transactions, including collaborations, asset acquisitions and/or licensing of third-party intellectual property rights. The company does not provide guidance regarding its GAAP effective tax rate because it is unable to forecast with reasonable certainty the impact of excess tax benefits related to stock-based compensation and the possibility of certain discrete items, which could be material.