On August 6, 2020 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported operational highlights and financial results for the second quarter ended June 30, 2020 (Press release, Intellia Therapeutics, AUG 6, 2020, View Source [SID1234563137]).

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"We are very pleased to announce our first regulatory submission to initiate a Phase 1 study of NTLA-2001, which is an important milestone as we deliver on our mission to develop curative, CRISPR/Cas9-based treatments for severe diseases. Our CTA keeps us on track to dose our first ATTR patient by year-end and is a critical step in executing our global development strategy for the first systemically delivered CRISPR-based therapy to enter clinical trial," said Intellia President and Chief Executive Officer, John Leonard, M.D. "With our recently expanded collaboration with Regeneron and subsequent financing, we are well-capitalized to advance our initial wave of development programs and continue our work developing innovative modular platform capabilities."

Second Quarter 2020 and Recent Operational Highlights

ATTR Program: Intellia announced today it has submitted its first Clinical Trial Application (CTA) to the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase 1 study of NTLA-2001 for the treatment of transthyretin amyloidosis (ATTR). Based on the Company’s in vivo liver knockout approach, NTLA-2001 is a potential single-course therapy for patients living with ATTR. Pending CTA authorization and subject to the impact of COVID-19, the Company is on track to dose its first patient by the end of 2020 with the first systemically delivered CRISPR/Cas9-based therapy to enter the clinic. The Company is submitting additional regulatory applications to enable enrollment in other countries as part of its global development strategy. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead development and commercialization party, and Regeneron Pharmaceuticals, Inc. (Regeneron).

AML Program: NTLA-5001 is a wholly owned, T cell receptor (TCR)-T cell therapy development candidate targeting the Wilms’ Tumor 1 (WT1) antigen for the treatment of acute myeloid leukemia (AML). The Company’s approach aims to develop a broadly applicable treatment for AML patients, regardless of the mutational subtypes of the cancer. At the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting, held from May 12-15, 2020, Intellia presented data on its proprietary T cell engineering process in support of NTLA-5001. The data showed that the Company’s proprietary process enables multiple, highly efficient, sequential edits in T cells, whether knocking out or inserting genes. This technology yields engineered cells with high anti-tumor activity and favorable attributes, including a desired memory phenotype, which is associated with longer-lasting treatment effects. Importantly, chromosomal translocations (i.e., undesired chromosomal rearrangements) were similar to background levels in untreated cells. Intellia continues to advance Investigational New Drug application (IND)-enabling activities and remains on track to submit an IND or IND-equivalent for NTLA-5001 in the first half of 2021. Additional efforts are underway to evaluate potential use of the WT1-targeted TCR construct to treat solid tumors.

HAE Program: NTLA-2002 is a wholly owned, in vivo development candidate for the treatment of hereditary angioedema (HAE). Building on Intellia’s modular lipid nanoparticle (LNP) delivery system, NTLA-2002 is designed to knock out the prekallikrein B1 (KLKB1) gene in the liver after a single course of treatment, which is expected to prevent improperly regulated bradykinin production and therefore, reduce HAE attacks. In a non-human primate (NHP) study of its lead LNP formulation for NTLA-2002, the knockout of KLKB1 resulted in a therapeutically relevant reduction of serum kallikrein levels and activity following a single dose. Consistent with the durability achieved in earlier NHP studies for its lead in vivo program, the Company has now demonstrated sustained kallikrein activity reduction for 10 months in an ongoing study. Based on these results, Intellia believes NTLA-2002 could be efficacious and durable in preventing HAE attacks following a single course of treatment. Intellia continues to progress IND-enabling activities and is on track to submit an IND or IND-equivalent for NTLA-2002 in the second half of 2021.
CRISPR/Cas9-mediated targeted transgene insertion and allogeneic cell solutions. Additionally, to supplement its ex vivo capabilities, the Company established research collaborations and license agreements with TeneoBio and GEMoaB GmbH to develop engineered cell therapies for immuno-oncology and autoimmune diseases. Intellia’s broad platform innovations and expanded capabilities will drive the next wave of in vivo and ex vivo clinical candidates.

Regeneron Collaboration: In June 2020, Intellia and Regeneron announced an expansion of their existing collaboration to co-develop potential products for the treatment of hemophilia A and B. The collaboration expansion builds upon the jointly-developed targeted transgene insertion capabilities designed to durably restore a missing protein and to overcome the limitations of traditional gene therapy. The collaboration also provides Regeneron with rights to develop products for additional in vivo CRISPR/Cas9-based therapeutic liver targets. Under the expansion, the term of the collaboration has been extended until April 2024, at which point Regeneron has an option to renew for an additional two years. In addition, the expansion grants Regeneron a royalty-bearing, non-exclusive license to certain Intellia intellectual property to develop and commercialize up to 10 ex vivo CRISPR/Cas9 products in defined cell types. Intellia received $100 million through an upfront payment of $70 million and an additional $30 million equity investment from Regeneron at $32.42 per share.

Financing: In June 2020, Intellia closed an underwritten public offering of 6,301,370 shares of common stock, including the exercise in full of the underwriters’ option to purchase additional shares, at the public offering price of $18.25 per share. Intellia received aggregate gross proceeds of approximately $115 million, before underwriting discounts and commissions and offering expenses.

Modular Platform: Intellia continues to make significant progress across its platform technologies, broadening the in vivo and ex vivo application of genome editing. This includes developing innovative

Upcoming Events

The Company will participate in the following events during the third quarter of 2020:
Wedbush PacGrow Healthcare Conference, August 11, Virtual

Baird Healthcare Conference, September 9, Virtual

Upcoming Milestones

The Company has set forth the following for pipeline progression:

ATTR: Plan to dose first patient by end of 2020

AML: Submit an IND or IND-equivalent for NTLA-5001 in 1H 2021

HAE: Submit an IND or IND-equivalent for NTLA-2002 in 2H 2021Second Quarter 2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $436.8 million as of June 30, 2020, compared to $284.5 million as of December 31, 2019. The increase was driven by net proceeds of $107.7 million from the June follow-on public offering, $100.0 million upfront payment from the Regeneron collaboration expansion, which included a $30.0 million equity investment, $14.7 million of net equity proceeds raised from the Company’s "At the Market" (ATM) agreement, $14.4 million of funding received under existing collaborations with Regeneron and Novartis and $2.1 million in proceeds from employee-based stock plans. These increases were offset in part by cash used to fund operations of approximately $86.5 million.

Collaboration Revenue: Collaboration revenue increased by $5.1 million to $16.3 million during the second quarter of 2020, compared to $11.1 million during the second quarter of 2019. The increase in collaboration revenue in 2020 was mainly driven by an $8.4 million one-time cumulative catch-up adjustment related to the extension of the Regeneron collaboration.

R&D Expenses: Research and development expenses increased by $12.3 million to $37.8 million during the second quarter of 2020, compared to $25.5 million during the second quarter of 2019. This increase was primarily driven by IND-enabling activities related to our lead programs, research personnel growth to support these programs, and the expansion of the development organization.

G&A Expenses: General and administrative expenses decreased by $1.6 million to $11.5 million during the second quarter of 2020, compared to $13.1 million during the second quarter of 2019. This decrease was primarily driven by a decrease in legal expenses, which were principally related to a decrease in certain activities related to intellectual property matters.

Net Loss: The Company’s net loss was $32.4 million for the second quarter of 2020, compared to $25.7 million during the second quarter of 2019.

Financial Guidance

Intellia expects that its cash, cash equivalents and marketable securities as of June 30, 2020 will enable the Company to fund its anticipated operating expenses and capital expenditure requirements at least through the

next 24 months. This expectation excludes any strategic use of capital not currently in the Company’s base-case planning assumptions.

Conference Call to Discuss Second Quarter 2020 Earnings

The Company will discuss these results on a conference call today, August 6, 2020, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-877-317-6789 and international callers should dial +1-412-317-6789, approximately five minutes before the call.

All participants should ask to be connected to the Intellia Therapeutics conference 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 www.intelliatx.com, beginning on August 6, 2020 at 12 p.m. ET.

On August 6, 2020 Adaptimmune Therapeutics plc (Nasdaq: ADAP), a leader in cell therapy to treat cancer, reported financial results and provided a business update for the second quarter ended June 30, 2020 (Press release, Adaptimmune, AUG 6, 2020, View Source [SID1234563136]).

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"We reported responses in multiple solid tumor types during the second quarter of 2020 demonstrating the potential of SPEAR T-cells to deliver benefit to people with cancer. We also raised capital, placing us in a solid financial position to continue executing on our strategic plans," said Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer. "Despite the impact of the COVID-19 pandemic on the biotech industry, we made good progress in our preparations toward launching our first product in the US in 2022 for patients with sarcoma, whilst initiating and planning new Phase 2 clinical trials. However, as we enter the second half of the year, we expect COVID-19 to continue to have an impact and are monitoring this evolving situation closely."

PLANNED MILESTONES 2H 2020

·Update on ADP-A2AFP Phase 1 trial at the International Liver Congress to be held virtually from August 27 to 29

oAn oral presentation entitled "Data from the third dose cohort of an ongoing study with ADP-A2AFP SPEAR T-cells" will be presented by Dr. Bruno Sangro of Clinica Universidad de Navarra

oA poster summarizing data from the first two cohorts of the ADP-A2AFP Phase 1 trial will be presented by Dr. Tim Meyer of University College London

·Updates on dose escalation cohorts from the SURPASS trial at a medical conference

·Durability and translational data from patients with synovial sarcoma from the ADP-A2M4 Phase 1 trial at a medical conference

·Investor Day to be held on November 20, 2020

CLINICAL UPDATES

·With timeline continuing to support 2022 launch in the US, enrollment in the Phase 2 SPEARHEAD-1 trial of ADP-A2M4, for patients with synovial sarcoma or myxoid / round cell liposarcoma (MRCLS), continues to progress

·The evolving COVID-19 pandemic continues to have an impact on clinical trials varying site-by-site and among countries

Phase 1 trials (ADP-A2AFP, radiation sub-study, and SURPASS) continue and patients are being enrolled and treated

·First site has been initiated and has started screening patients for the SPEARHEAD-2 Phase 2 clinical trial, combining ADP-A2M4 with pembrolizumab for people with head and neck cancer

·Protocol design for the Phase 2 trial with ADP-A2M4CD8 in gastroesophageal cancers has commenced and sites are being identified. The Company plans to initiate this trial in the first half of 2021

PROGRESS TOWARD GOAL OF LAUNCHING ADP-A2M4 IN SARCOMA IN THE US IN 2022

·Granted access to PRIME regulatory support by the EMA further confirming the potential of ADP-A2M4 to treat people with advanced sarcoma, along with the previously granted Orphan Drug Designation (ODD) in Europe, as well as the FDA’s ODD and Regenerative Medicine Advanced Therapy designation

MANUFACTURING AND SUPPLY

·The Company has focused on manufacturing SPEAR T-cells for patients in the SPEARHEAD-1 trial and increasing capacity to provide for all ongoing and planned trials

·Scaling up personnel, manufacturing processes and IT systems, and optimizing space in our Navy Yard facility in preparation for commercial launch in sarcoma

·Following receipt of a Certificate of GMP Compliance from the MHRA for its vector manufacturing operations in July, the Company began using lentiviral vector produced in-house at its dedicated manufacturing space within the Cell and Gene Therapy Catapult Manufacturing Centre at Stevenage, UK for select clinical trials

FUNDING

·Underwritten public offering closed on June 4, 2020 generating net proceeds of approximately $244 million

Financial Results for the three and six month periods ended June 30, 2020

·Cash / liquidity position: As of June 30, 2020, Adaptimmune had cash and cash equivalents of $122.4 million and Total Liquidity1 of $419.0 million.

·Revenue: Revenue for the three and six months ended June 30, 2020 was $0.5 million and $1.3 million, respectively, compared to $0.2 million for both of the same periods in 2019. The increase in revenue is mainly due to further development of the third target nominated by GSK under the GSK Collaboration and License Agreement.

·Research and development (R&D) expenses: R&D expenses for the three and six months ended June 30, 2020 were $20.5 million and $41.7 million, respectively, compared to $25.5 million and $47.5 million for the same periods in 2019. The decreases in both periods are primarily due to lower development costs brought about by COVID-19 delays, a reduction in the average number of employees engaged in research and development, and in-process research and development costs of $2.0m in 2019 as a result of entering into a collaboration agreement with Alpine Immune Sciences, Inc.

·General and administrative (G&A) expenses: G&A expenses for the three and six months ended June 30, 2020 were $10.3 million and $19.6 million, respectively, compared to $10.1 million and $21.9 million for the same periods in 2019. The decrease in the six months ended June 30, 2020 was primarily driven by reduced travel costs and share-based compensation expense, partially offset by an increase in costs associated with commercialization. We expect that our general and administrative expenses will increase in the future as we expand our operations and move towards commercial launch.

·Other (expense) income, net: Other (expense) income, net for the three and six months ended June 30, 2020 was an expense of $0.7 million and income of $0.2 million, respectively, compared to expenses of $6.3 million and $0.8 million for the same periods in 2019. Other (expense) income, net primarily comprises unrealized foreign exchange movements, which fluctuate depending on exchange rates and the amount of foreign currency assets and liabilities.

·Net loss: Net loss attributable to holders of the Company’s ordinary shares for the three and six months ended June 30, 2020 was $29.9 million and $58.0 million, respectively, and $(0.04) and $(0.07) per ordinary share, respectively, compared to $41.1 million and $68.5 million and $(0.07) and $(0.11) per ordinary share for the same periods in 2019.

Financial guidance

The Company believes that its existing cash, cash equivalents and marketable securities will fund the Company’s current operations into 2022, as further detailed in the Company’s Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2020, to be filed with the Securities and Exchange Commission following this earnings release.

1 Total liquidity is a non-GAAP financial measure, which is explained and reconciled to the most directly comparable financial measures prepared in accordance with GAAP below.

Conference Call and Webcast Information

The Company will host a live teleconference at 8:00 a.m. EDT (1:00 p.m. BST) today, August 6, 2020. The live webcast of the conference call will be available in the investor section of Adaptimmune’s corporate website at www.adaptimmune.com. An archive will be available after the call at the same address. To participate in the live conference call, please dial (833) 652-5917 (U.S. or Canada) or +1 (430) 775-1624 (International). After placing the call, please ask to be joined into the Adaptimmune conference call and provide the confirmation code (5488705).

On August 6, 2020 InflaRx N.V. (Nasdaq: IFRX), a clinical-stage biopharmaceutical company developing anti-inflammatory therapeutics by targeting the complement system, reported that it will present at several upcoming virtual investor events in August and September as follows (Press release, InflaRx, AUG 6, 2020, View Source [SID1234563135]):

BTIG Virtual Biotechnology Conference: August 10th – 11th

A BTIG analyst will host a fireside chat with Prof. Niels C. Riedemann, Chief Executive Officer and Founder of InflaRx, to discuss the Company’s pipeline and upcoming catalysts on Monday, August 10th at 12:30pm EST. The Company will also hold virtual 1X1 meetings.

A live webcast of the fireside chat will be provided on the InflaRx website in the Investors section under Events & Presentations. A replay will be available following the live event.

H.C. Wainwright Annual Global Investment Conference: September 14th – 16th

The Company will give a presentation and conduct virtual 1X1 meetings.

A live webcast of the Company’s presentation will be provided on the InflaRx website in the Investors section under Events & Presentations.

Oppenheimer Fall Healthcare Life Sciences & MedTech Summit: September 21st – 23rd

The Company will give a presentation and conduct virtual 1X1 meetings.

About IFX-1:

IFX-1 is a first-in-class monoclonal anti-human complement factor C5a antibody, which highly and effectively blocks the biological activity of C5a and demonstrates high selectivity towards its target in human blood. Thus, IFX-1 leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5. IFX-1 has been demonstrated to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key "amplifier" of this response in pre-clinical studies. IFX-1 is believed to be the first monoclonal anti-C5a antibody introduced into clinical development. Approximately 300 people have been treated with IFX-1 in clinical trials, and the antibody has been shown to be well tolerated. IFX-1 is currently being developed for various indications, including Hidradenitis Suppurativa, ANCA-associated vasculitis, Pyoderma Gangraenosum and COVID-19 pneumonia.

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On August 6, 2020 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare disease reported financial results for the second quarter ended June 30, 2020, and provided a business update (Press release, Insmed, AUG 6, 2020, View Source [SID1234563134]).

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"I am incredibly proud of the Insmed team’s performance in the second quarter of 2020, which saw significant progress across our programs even against the backdrop of the continued COVID-19 pandemic," commented Will Lewis, Chair and Chief Executive Officer of Insmed. "ARIKAYCE U.S. sales showed strong sequential growth from the first quarter as we continued to support patients and physicians through both virtual and in-person efforts, and we are excited about its inclusion in the new international treatment guidelines as well as the recent positive CHMP opinion. At the same time, we continued to advance brensocatib, which we believe offers a significant opportunity to address unmet needs in bronchiectasis and other neutrophil-driven diseases, along with our earlier-stage clinical pipeline."

Second Quarter 2020 Financial Results

·Total revenue for the second quarter ended June 30, 2020, was $42.5 million, comprising U.S. net sales of $41.0 million and ex-U.S. net sales of $1.5 million. This compares to total revenue of $30.0 million for the second quarter of 2019.

·Cost of product revenues (excluding amortization of intangible assets) was $10.0 million for the second quarter of 2020, compared to $4.9 million for the second quarter of 2019.

·Research and development (R&D) expenses were $35.7 million for the second quarter of 2020, compared to $33.5 million for the second quarter of 2019.

·Selling, general, and administrative (SG&A) expenses for the second quarter of 2020 were $49.7 million, compared to $52.4 million for the second quarter of 2019.

For the second quarter of 2020, Insmed reported a GAAP net loss of $61.9 million, or $0.64 per share, compared to a GAAP net loss of $66.5 million, or $0.81 per share, for the second quarter of 2019.

·During the second quarter of 2020, Insmed completed a public offering of 11,155,000 shares of common stock, including 1,455,000 shares issued pursuant to the exercise in full of the underwriters’ option to purchase additional shares, that resulted in net cash proceeds of $245.9 million, after deducting underwriting discounts and other offering-related expenses.

Recent Corporate Developments & Program Highlights

Brensocatib Advancement

Insmed presented final results from the Phase 2 WILLOW study of brensocatib in patients with non-cystic fibrosis bronchiectasis (NCFBE) during a virtual session of the American Thoracic society in June 2020. Also in June, Insmed received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for brensocatib for the treatment of adult patients with NCFBE for reducing exacerbations. The Company remains on track to initiate its planned Phase 3 program with brensocatib in patients with bronchiectasis by the end of 2020.

ARIKAYCE Global Advancement

In July 2020, Insmed received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) recommending ARIKAYCE Liposomal 590 mg Nebuliser Dispersion for the treatment of nontuberculous mycobacterial (NTM) lung infections caused by Mycobacterium avium complex (MAC) in non-CF patients with limited treatment options. Pending approval of the marketing authorization application by the European Commission (EC), the Company anticipates a potential launch in Germany by the end of 2020, followed shortly thereafter by the UK.

Insmed has also submitted a new drug application for ARIKAYCE to Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of patients with NTM lung disease caused by MAC who did not sufficiently respond to prior treatment. In June 2020, a Japanese Medical Device Notification (JMDN) was submitted to the MHLW for Lamira, the designated device for administration of ARIKAYCE. The JMDN was accepted and Lamira is authorized for use in Japan.

New International NTM Treatment Guidelines

In July 2020, the American Thoracic Society, European Respiratory Society, European Society of Clinical Microbiology and Infectious Diseases, and Infectious Diseases Society of America issued new treatment guidelines for the management of NTM lung disease. The guidelines strongly recommend the addition of ARIKAYCE to the standard treatment regimen for patients with MAC lung disease who have failed to convert to a negative sputum culture after at least six months of treatment.

ARIKAYCE Label Expansion

Insmed continues to advance the post-approval confirmatory clinical trial for ARIKAYCE in a front-line setting of patients with MAC lung disease as well as the development of an appropriate patient reported outcome (PRO) tool that will enable the assessment of ARIKAYCE for the treatment of NTM lung disease. Insmed plans to initiate both the confirmatory study and a study to validate the PRO by the end of 2020 and to run these studies in parallel, pending alignment with the FDA.

Treprostinil Palmitil Advancement

Insmed is advancing treprostinil palmitil, a dry powder, inhaled treprostinil prodrug formulation, for the potential treatment of pulmonary arterial hypertension and plans to initiate a Phase 1 study by the end of 2020.

Balance Sheet

As of June 30, 2020, Insmed had cash and cash equivalents of $641.9 million. The Company’s total operating expenses for the second quarter of 2020 were $86.7 million. Adjusted operating expenses, as defined below, for the second quarter of 2020 were $73.7 million.

The Company plans to continue investing in the following key activities in 2020:

(i)U.S. commercialization of ARIKAYCE;

(ii)clinical trial activities, including (a) the development of a PRO for NTM lung disease, the initiation of a study to validate the PRO and, in parallel, a confirmatory clinical study of ARIKAYCE, (b) the advancement of brensocatib into a Phase 3 program in patients with bronchiectasis, and (c) the advancement of treprostinil palmitil; and

(iii)expansion in Japan and Europe to support pre-commercial activities for ARIKAYCE in those regions and, pending approval of the marketing authorization application by the EC, launch activities in initial European countries.

Conference Call

Insmed will host a conference call beginning today at 8:30 AM Eastern Time. Shareholders and other interested parties may participate in the conference call by dialing (888) 317-6003 (domestic) or (412) 317-6061 (international) and referencing conference ID number 9359069. The call will also be webcast live on the company’s website at www.insmed.com.

A replay of the conference call will be accessible approximately one hour after its completion through August 20, 2020 by dialing (877) 344-7529 (domestic) or (412) 317-0088 (international) and referencing replay access code 10146257. A webcast of the call will also be archived for 90 days under the Investor Relations section of the company’s website at www.insmed.com.

Non-GAAP Financial Measures

In addition to the U.S. generally accepted accounting principles (GAAP) results, this earnings release includes adjusted operating expenses, a non-GAAP financial measure, which Insmed defines as total operating expenses less stock-based compensation expense, depreciation, amortization of intangibles and certain milestones related to ARIKAYCE, which are payable under our amended agreements with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT). A reconciliation of this non-GAAP financial measure to its most directly comparable GAAP financial measure is presented in the table attached to this press release.

Management believes that this non-GAAP financial measure is useful to both management and investors in analyzing our ongoing business and operating performance. Management believes that providing this non-GAAP information to investors, in addition to the GAAP results, allows investors to view our financial results in the way that management views financial results. Management does not intend the presentation of this non-GAAP financial measure to be considered in isolation or as a substitute for results prepared in accordance with GAAP. In addition, this non-GAAP financial measure may differ from similarly named measures used by other companies.

About ARIKAYCE (amikacin liposome inhalation suspension)

ARIKAYCE is the first and only FDA-approved therapy indicated for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options. Current international treatment guidelines recommend the use of ARIKAYCE in combination with a multidrug regimen in patients with MAC lung disease who have failed standard therapy after at least six months of treatment. ARIKAYCE is a novel, inhaled, once-daily formulation of amikacin, an established antibiotic that was historically administered intravenously and associated with severe toxicity to hearing, balance, and kidney function. Insmed’s proprietary PULMOVANCE liposomal technology enables the delivery of amikacin directly to the lungs, where liposomal amikacin is taken up by lung macrophages where the infection resides, while limiting systemic exposure. ARIKAYCE is administered once daily using the Lamira Nebulizer System manufactured by PARI Pharma GmbH (PARI).

About PARI Pharma and the Lamira Nebulizer System

ARIKAYCE (amikacin liposome inhalation suspension) is delivered by a novel inhalation device, the Lamira Nebulizer System, developed by PARI. Lamira is a quiet, portable nebulizer that enables efficient aerosolization of liquid medications, including liposomal formulations such as ARIKAYCE, via a vibrating, perforated membrane. Based on PARI’s 100-year history working with aerosols, PARI is dedicated to advancing inhalation therapies by developing innovative delivery platforms and new pharmaceutical formulations that work together to improve patient care.

About Brensocatib

Brensocatib is a small molecule, oral, reversible inhibitor of dipeptidyl peptidase I (DPP1) being developed by Insmed for the treatment of patients with bronchiectasis. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs.

Hypersensitivity Pneumonitis has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate.
U.S. INDICATION

LIMITED POPULATION: ARIKAYCEÒ is indicated in adults, who have limited or no alternative treatment options, for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options. This drug is indicated for use in a limited and specific population of patients.
This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Limitation of Use: ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.

Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088. You can also call the Company at 1-844-4-INSMED.

Hemoptysis has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (17.9%) compared to patients treated with a background regimen alone (12.5%). If hemoptysis occurs, manage patients as medically appropriate.

Bronchospasm has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (28.7%) compared to patients treated with a background regimen alone (10.7%). If bronchospasm occurs during the use of ARIKAYCE, treat patients as medically appropriate.

Exacerbations of underlying pulmonary disease has been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease (COPD), infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (14.8%) compared to patients treated with background regimen alone (9.8%). If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat patients as medically appropriate.

Anaphylaxis and Hypersensitivity Reactions: Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures.

Ototoxicity has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE plus background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (7.6% in ARIKAYCE plus background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background regimen vs 2.7% in the background regimen alone arm). Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage patients as medically appropriate, including potentially discontinuing ARIKAYCE.

Nephrotoxicity was observed during the clinical trials of ARIKAYCE in patients with MAC lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE.

Neuromuscular Blockade: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Patients with known or suspected neuromuscular disorders, such as myasthenia gravis, should be closely monitored since aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions.

Embryo-Fetal Toxicity: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. Patients who use ARIKAYCE during pregnancy, or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus.

Most Common Adverse Reactions: The most common adverse reactions in Trial 1 at an incidence ≥5% for patients using ARIKAYCE plus background regimen compared to patients treated with background regimen alone were dysphonia (47% vs 1%), cough (39% vs 17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%), ototoxicity (17% vs 10%), upper airway irritation (17% vs 2%), musculoskeletal pain (17% vs 8%), fatigue and asthenia (16% vs 10%), exacerbation of underlying pulmonary disease (15% vs 10%), diarrhea (13% vs 5%), nausea (12% vs 4%), pneumonia (10% vs 8%), headache (10% vs 5%), pyrexia (7% vs 5%), vomiting (7% vs 4%), rash (6% vs 2%), decreased weight (6% vs 1%), change in sputum (5% vs 1%), and chest discomfort (5% vs 3%).

Drug Interactions: Avoid concomitant use of ARIKAYCE with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity. Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol.

Overdosage: Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute toxicity should be treated with immediate withdrawal of ARIKAYCE, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing amikacin from the body. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment.

On August 6, 2020 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported operational highlights and financial results for the second quarter ended June 30, 2020 (Press release, Intellia Therapeutics, AUG 6, 2020, View Source [SID1234563133]).

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"We are very pleased to announce our first regulatory submission to initiate a Phase 1 study of NTLA-2001, which is an important milestone as we deliver on our mission to develop curative, CRISPR/Cas9-based treatments for severe diseases. Our CTA keeps us on track to dose our first ATTR patient by year-end and is a critical step in executing our global development strategy for the first systemically delivered CRISPR-based therapy to enter clinical trial," said Intellia President and Chief Executive Officer, John Leonard, M.D. "With our recently expanded collaboration with Regeneron and subsequent financing, we are well-capitalized to advance our initial wave of development programs and continue our work developing innovative modular platform capabilities."

Second Quarter 2020 and Recent Operational Highlights

ATTR Program: Intellia announced today it has submitted its first Clinical Trial Application (CTA) to the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) to initiate a Phase 1 study of NTLA-2001 for the treatment of transthyretin amyloidosis (ATTR). Based on the Company’s in vivo liver knockout approach, NTLA-2001 is a potential single-course therapy for patients living with ATTR. Pending CTA authorization and subject to the impact of COVID-19, the Company is on track to dose its first patient by the end of 2020 with the first systemically delivered CRISPR/Cas9-based therapy to enter the clinic. The Company is submitting additional regulatory applications to enable enrollment in other countries as part of its global development strategy. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead development and commercialization party, and Regeneron Pharmaceuticals, Inc. (Regeneron).
AML Program: NTLA-5001 is a wholly owned, T cell receptor (TCR)-T cell therapy development candidate targeting the Wilms’ Tumor 1 (WT1) antigen for the treatment of acute myeloid leukemia (AML). The Company’s approach aims to develop a broadly applicable treatment for AML patients, regardless of the mutational subtypes of the cancer. At the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) Annual Meeting, held from May 12-15, 2020, Intellia presented data on its proprietary T cell engineering process in support of NTLA-5001. The data showed that the Company’s proprietary process enables multiple, highly efficient, sequential edits in T cells, whether knocking out or inserting genes. This technology yields engineered cells with high anti-tumor activity and favorable attributes, including a desired memory phenotype, which is associated with longer-lasting treatment effects. Importantly, chromosomal translocations (i.e., undesired chromosomal rearrangements) were similar to background levels in untreated cells. Intellia continues to advance Investigational New Drug application (IND)-enabling activities and remains on track to submit an IND or IND-equivalent for NTLA-5001 in the first half of 2021. Additional efforts are underway to evaluate potential use of the WT1-targeted TCR construct to treat solid tumors.
HAE Program: NTLA-2002 is a wholly owned, in vivo development candidate for the treatment of hereditary angioedema (HAE). Building on Intellia’s modular lipid nanoparticle (LNP) delivery system, NTLA-2002 is designed to knock out the prekallikrein B1 (KLKB1) gene in the liver after a single course of treatment, which is expected to prevent improperly regulated bradykinin production and therefore, reduce HAE attacks. In a non-human primate (NHP) study of its lead LNP formulation for NTLA-2002, the knockout of KLKB1 resulted in a therapeutically relevant reduction of serum kallikrein levels and activity following a single dose. Consistent with the durability achieved in earlier NHP studies for its lead in vivo program, the Company has now demonstrated sustained kallikrein activity reduction for 10 months in an ongoing study. Based on these results, Intellia believes NTLA-2002 could be efficacious and durable in preventing HAE attacks following a single course of treatment. Intellia continues to progress IND-enabling activities and is on track to submit an IND or IND-equivalent for NTLA-2002 in the second half of 2021.
Modular Platform: Intellia continues to make significant progress across its platform technologies, broadening the in vivo and ex vivo application of genome editing. This includes developing innovative CRISPR/Cas9-mediated targeted transgene insertion and allogeneic cell solutions. Additionally, to supplement its ex vivo capabilities, the Company established research collaborations and license agreements with TeneoBio and GEMoaB GmbH to develop engineered cell therapies for immuno-oncology and autoimmune diseases. Intellia’s broad platform innovations and expanded capabilities will drive the next wave of in vivo and ex vivo clinical candidates.
Regeneron Collaboration: In June 2020, Intellia and Regeneron announced an expansion of their existing collaboration to co-develop potential products for the treatment of hemophilia A and B. The collaboration expansion builds upon the jointly-developed targeted transgene insertion capabilities designed to durably restore a missing protein and to overcome the limitations of traditional gene therapy. The collaboration also provides Regeneron with rights to develop products for additional in vivo CRISPR/Cas9-based therapeutic liver targets. Under the expansion, the term of the collaboration has been extended until April 2024, at which point Regeneron has an option to renew for an additional two years. In addition, the expansion grants Regeneron a royalty-bearing, non-exclusive license to certain Intellia intellectual property to develop and commercialize up to 10 ex vivo CRISPR/Cas9 products in defined cell types. Intellia received $100 million through an upfront payment of $70 million and an additional $30 million equity investment from Regeneron at $32.42 per share.
Financing: In June 2020, Intellia closed an underwritten public offering of 6,301,370 shares of common stock, including the exercise in full of the underwriters’ option to purchase additional shares, at the public offering price of $18.25 per share. Intellia received aggregate gross proceeds of approximately $115 million, before underwriting discounts and commissions and offering expenses.
Upcoming Events

The Company will participate in the following events during the third quarter of 2020:

Wedbush PacGrow Healthcare Conference, August 11, Virtual
Baird Healthcare Conference, September 9, Virtual
Upcoming Milestones

The Company has set forth the following for pipeline progression:

ATTR: Plan to dose first patient by end of 2020
AML: Submit an IND or IND-equivalent for NTLA-5001 in 1H 2021
HAE: Submit an IND or IND-equivalent for NTLA-2002 in 2H 2021
Second Quarter 2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $436.8 million as of June 30, 2020, compared to $284.5 million as of December 31, 2019. The increase was driven by net proceeds of $107.7 million from the June follow-on public offering, $100.0 million upfront payment from the Regeneron collaboration expansion, which included a $30.0 million equity investment, $14.7 million of net equity proceeds raised from the Company’s "At the Market" (ATM) agreement, $14.4 million of funding received under existing collaborations with Regeneron and Novartis and $2.1 million in proceeds from employee-based stock plans. These increases were offset in part by cash used to fund operations of approximately $86.5 million.
Collaboration Revenue: Collaboration revenue increased by $5.1 million to $16.3 million during the second quarter of 2020, compared to $11.1 million during the second quarter of 2019. The increase in collaboration revenue in 2020 was mainly driven by an $8.4 million one-time cumulative catch-up adjustment related to the extension of the Regeneron collaboration.
R&D Expenses: Research and development expenses increased by $12.3 million to $37.8 million during the second quarter of 2020, compared to $25.5 million during the second quarter of 2019. This increase was primarily driven by IND-enabling activities related to our lead programs, research personnel growth to support these programs, and the expansion of the development organization.
G&A Expenses: General and administrative expenses decreased by $1.6 million to $11.5 million during the second quarter of 2020, compared to $13.1 million during the second quarter of 2019. This decrease was primarily driven by a decrease in legal expenses, which were principally related to a decrease in certain activities related to intellectual property matters.
Net Loss: The Company’s net loss was $32.4 million for the second quarter of 2020, compared to $25.7 million during the second quarter of 2019.
Financial Guidance

Intellia expects that its cash, cash equivalents and marketable securities as of June 30, 2020 will enable the Company to fund its anticipated operating expenses and capital expenditure requirements at least through the next 24 months. This expectation excludes any strategic use of capital not currently in the Company’s base-case planning assumptions.

Conference Call to Discuss Second Quarter 2020 Earnings

The Company will discuss these results on a conference call today, August 6, 2020, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-877-317-6789 and international callers should dial +1-412-317-6789, approximately five minutes before the call.
All participants should ask to be connected to the Intellia Therapeutics conference 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 www.intelliatx.com, beginning on August 6, 2020 at 12 p.m. ET.