On May 7, 2019 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, reported financial results for the first quarter ended March 31, 2019 and provided a business update (Press release, Insmed, MAY 7, 2019, View Source [SID1234535801]).

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"We are very excited about the progress this quarter with the U.S. launch of ARIKAYCE (amikacin liposome inhalation suspension), the first and only FDA-approved treatment for patients with refractory MAC lung disease, including steady increases in new patients and prescribers, strong anecdotal feedback from the MAC lung disease community, and positive payer trends," commented Will Lewis, Chairman and Chief Executive Officer of Insmed. "In line with our strategic priorities, we are continuing to work with the FDA on the design of a post-marketing confirmatory study of ARIKAYCE, which is required for the full U.S. approval of ARIKAYCE and will be conducted in a frontline setting; continuing our global expansion to support potential regulatory filings for ARIKAYCE in Europe and Japan; and building and advancing a promising pipeline with the potential to bring much-needed therapies to patients with serious and rare diseases."

First Quarter 2019 Financial Results

·Total revenue for the first quarter ended March 31, 2019 was $21.9 million, comprising U.S. net sales of $21.0 million and ex-U.S. net sales of $0.9 million. The ex-U.S. net product sales include $0.8 million from the Temporary Authorization for Use (Autorisation Temporaire d’Utilisation or ATU) program in France and $0.1 million from the named patient program in Germany, both compassionate use programs.

· Cost of product revenues (excluding amortization of intangible assets) was $4.2 million for the first quarter of 2019.

Research and development expenses were $31.2 million for the first quarter of 2019, compared with $30.1 million for the first quarter of 2018.

· Selling, general and administrative expenses for the first quarter of 2019 were $54.8 million, compared with $32.7 million for the first quarter of 2018. The increase was primarily due to an increase in headcount, including the hiring of our field force, and

higher expenses related to commercial activities for ARIKAYCE, including non-branded disease awareness, patient support activities, and field operations.

· For the first quarter of 2019, Insmed reported a net loss of $74.2 million, or $0.96 per share, compared with a net loss of $68.5 million, or $0.89 per share, for the first quarter of 2018.

Recent Corporate Developments & Program Highlights

Strong Start to U.S. ARIKAYCE Launch

ARIKAYCE was granted accelerated approval by the U.S. Food and Drug Administration (FDA) on September 28, 2018, for the treatment of refractory Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients who have limited or no alternative treatment options.

The Company expects to complete the design and protocol of the confirmatory clinical study during the first half of 2019 required for the full U.S. approval of ARIKAYCE by the FDA, which is intended to support the use of ARIKAYCE in a front-line setting for patients with MAC lung disease.

Data from Phase 3 CONVERT Study Accepted as Late-Breaker at ATS

Insmed announced in April that data on the sustainability and durability of culture conversion from the Phase 3 CONVERT Study of ARIKAYCE will be presented in a late-breaking oral session at the American Thoracic Society (ATS) International Conference on May 20, 2019. Additional data on ARIKAYCE as well as on Insmed’s pipeline candidates will also be presented at the meeting, taking place May 17-22 in Dallas.

Additional U.S. Patent Granted for ARIKAYCE

In April, the U.S. Patent and Trademark Office issued its 10th patent to Insmed for ARIKAYCE in MAC lung disease. The claims of the patent relate in part to methods for treating MAC lung disease via administration of ARIKAYCE to patients previously unresponsive to MAC therapy. This is the second U.S. patent for ARIKAYCE that provides intellectual property protection through 2035.

Global Expansion Under Way

Insmed is continuing its global expansion efforts to support potential regulatory filings for ARIKAYCE in Europe in mid-2019 and in Japan in the first half of 2020. The Company has hired Neil Hughes as Head of Europe, Middle East and Africa, effective June 1, to advance our launch preparations in Europe. Mr. Hughes joins Insmed from Shire, where he most recently served as general manager of endocrinology.

The Company is also progressing with the buildout of its new, state-of-the-art corporate headquarters in Bridgewater, NJ, with an anticipated move during the second half of 2019.

Insmed continues to invest in the buildout of an additional third-party manufacturing facility with Patheon UK Limited to increase the long-term production capacity for ARIKAYCE commercial inventory.

Enrollment Target Reached for WILLOW Study

Insmed has reached its enrollment target of 240 patients in the six-month Phase 2 WILLOW study of INS1007 for patients with non-CF bronchiectasis. The Company also plans to advance INS1007 into Phase 2 trials for the potential treatment of granulomatosis with polyangiitis (GPA).

Financial Guidance and Balance Sheet

As of March 31, 2019, Insmed had cash and cash equivalents of $420.2 million. The Company’s total costs and expenses for the first quarter of 2019 were $91.4 million, compared with total costs and expenses for the first quarter of 2018 of $62.8 million. The cash-based operating expenses for the first quarter of 2019 were $78.0 million, compared with cash-based operating expenses for the first quarter of 2018 of $56.3 million.

The Company now expects full-year 2019 revenues for ARIKAYCE to be in the range of $90 million to $105 million.

The Company plans to continue to invest in the following key activities in 2019:

(i)continued support of the U.S. launch and commercialization of ARIKAYCE;

(ii)clinical trials including (a) the ARIKAYCE post-marketing confirmatory study, which will be conducted in a front-line setting, (b) the six-month Phase 2 WILLOW study of INS1007 in patients with non-CF bronchiectasis, and (c) the advancement of other pipeline programs including INS1009 and our earlier-stage research pipeline;

(iii)global expansion in Europe and Japan to support potential regulatory filings and pre-commercial activities in those regions; and

(iv) buildout of an additional third-party manufacturing facility to increase long-term production capacity for ARIKAYCE and a new corporate headquarters facility.

As a result of these activities, Insmed continues to expect cash-based operating expenses to be in the range of $150 million to $170 million for the first half of 2019. In addition, the Company expects capital expenditures, including spend related to the buildout of a new corporate headquarters facility as well as payments classified within other assets for the future right-of-use asset related to the buildout of an additional third-party manufacturing facility, to be in the range of $25 million to $35 million for the first half of 2019.

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 1-888-317-6003

(domestic) or 1-412-317-6061 (international) and referencing conference ID number 6243203. 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 May 14, 2019 by dialing 1-877-344-7529 (domestic) or 1-412-317-0088 (international) and referencing replay access code 10131112. 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 cash-based operating expenses, a non-GAAP financial measure, which Insmed defines as total costs and expenses excluding cost of product revenues, stock-based compensation expense, depreciation and amortization of intangibles. 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 presentation, 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 MAC Lung Disease

Mycobacterium avium complex (MAC) lung disease is a rare and serious disorder that can significantly increase morbidity and mortality. Patients with MAC lung disease can experience a range of symptoms that often worsen over time, including chronic cough, dyspnea, fatigue, fever, weight loss, and chest pain. In some cases, MAC lung disease can cause severe, even permanent damage to the lungs, and can be fatal.

MAC lung disease is an emerging public health concern worldwide with significant unmet needs. Current guideline-based treatment involves the use of multi-drug regimens that are not specifically approved for MAC lung disease. The course of treatment is often two years or more and is inadequate in treating the disease in many patients.

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. 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. This approach prolongs the release of amikacin in the lungs 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.

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS

ARIKAYCE has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.

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.

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.

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.

Contraindications: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside.

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.

INDICATION

LIMITED POPULATION: ARIKAYCE 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 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.

On May 7, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported additional positive interim safety and efficacy data from its ongoing open label, single arm Phase 1/2 study of Annamycin in Poland (Press release, Moleculin, MAY 7, 2019, View Source [SID1234535842]). After receiving a single starting dose of 120 mg/m2 in the first cohort of the dose escalation phase of the trial, 2 of 3 patients treated responded sufficiently to qualify for a potentially curative bone marrow transplant. The results for all 3 patients were reviewed by the Safety Review Committee, which determined that no drug-related adverse events were observed that would prevent advancing the trial to the next higher dose level of 150 mg/m2. To date in the European trial, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other adverse events related to Annamycin have been reported. No additional patient data have been developed in the Company’s parallel US clinical trial, which is currently recruiting its second cohort to be given a dose level of 120 mg/m2 (the US trial started at a lower initial dose of 100 mg/m2).

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Moleculin Biotech, Inc. is a clinical-stage pharmaceutical company focused on the treatment of highly resistant cancers. (PRNewsfoto/Moleculin Biotech, Inc.)

"The progress in Europe, specifically Poland, continues to be encouraging," commented Walter Klemp, Moleculin’s Chairman and CEO. "In just a few months, we have completed the first cohort and we’ve seen a partial response from 2 out of 3 patients sufficient to qualify them for a potentially curative bone marrow transplant. It’s important to remember that these are relapsed or refractory patients for whom the standard of care failed. So, to see this kind of response at the starting dose level in the dose-ranging phase, we believe is quite remarkable. And, although this data is still preliminary and may not be indicative of the ultimate outcome of the trial, the improvement in activity at 120 mg/m2 in Poland as compared with the 100 mg/m2 cohort in the US is consistent with our expectations for Annamycin."

Mr. Klemp continued: "Recognizing that cardiotoxicity is a significant limitation of existing therapies, we are pleased that we continue to see no evidence of cardiotoxicity in any of the patients treated thus far. Specifically, there was no observed reduction in left ventricle ejection fraction, which is the standard metric for acute cardiotoxicity, nor any change in biomarkers that would indicate the potential for long-term cardiovascular impairment. This is an important step in the ongoing clinical study of Annamycin and toward our goal of ultimately demonstrating the drug’s safety and effectiveness to support regulatory approval in both the US and European Union."

Dr. Robert Shepard, Moleculin’s Chief Medical Officer for Annamycin added: "With the Polish trial now progressing to 150 mg/m2, we expect to see even better results. And, although 150 mg/m2 was the maximum tolerable dose established by the prior developer of Annamycin due to the incidence of mucositis in patients above that dose level, now that the cryotherapy protocol is well understood to mitigate the potential for dose-limiting mucositis, there is a good opportunity for dose levels to progress even beyond 150 mg/m2, so the potential to help patients is very exciting."

Study Design

The Company is studying Annamycin in both the US and Poland in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. The US and Polish trials have the same study design, consisting of a Phase 1 intended to establish a "Recommended Phase 2 Dose" ("RP2D"), to which the studies will then proceed. The Phase 1 studies provide for escalating doses in cohorts of 3 patients each, with each successive cohort receiving the next higher dose level until "dose limiting toxicities" prevent further increases. Cohort 1 in Poland received a dose of 120 mg/m2, and the results permit moving to 150 mg/m2. Cohort 1 in the US started at 100 mg/m2, and the results support moving to 120 mg/m2, and the Company is now seeking patients for the second cohort in both studies. (Because one patient in US cohort 1 did not complete the evaluation protocol, a fourth patient was added to complete that cohort.) Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.

We plan to report top-line results by cohort in each trial, with each announcement also including an update on the other trial. Top-line results will include reporting of any drug-related adverse events ("AEs") and assessment of cardiotoxicity, including Echo or MUGA scans measuring change in ejection fraction and measuring blood troponin level, which is considered a biomarker for potential long-term cardiovascular impairment. To date, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other drug-related AEs have been reported. Also, no loss of ejection fraction or reduction in Troponin levels has been reported. Top-line results will also include the number of partial responses ("PRs"), complete responses ("CRs") and patients deemed capable of progressing to a potentially curative bone marrow transplant, which we term "bridge to transplant" ("BTs"), each of which is essentially a function of the magnitude of reduction in a patient’s bone marrow blasts. For purposes of these clinical trials, a CR means, primarily, that the patient’s bone marrow blasts reduced to 5% or less, a PR means the patient’s bone marrow blasts reduced, but not to the level of a CR, and a BT means patients are deemed capable of progressing to a potentially curative bone marrow transplant. To date, there have been no PRs, CRs or BTs in the US trial, which has treated 4 patients at 100 mg/m2, and 2 PRs and BTs out of 3 patients treated in the Polish trial at 120 mg/m2.

The US trial also differs from the Polish trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2. The Company believes that the additional patient safety data gained from the Polish trial may also assist in the FDA’s review of cardiac safety.

On March 7, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage oncology therapeutics company, using a precision medicine approach to develop drugs that target cell division (mitosis) for the treatment of leukemias, lymphomas and solid tumor cancers, reported company highlights and financial results for the first quarter ended March 31, 2019 (Press release, Trovagene, MAY 7, 2019, View Source [SID1234535858]). The company is issuing this press release in lieu of conducting a conference call.

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"We are pleased with our accomplishments year-to-date, and our onvansertib clinical development programs continue to advance as planned," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "We began the year with presentation of data from our Phase 2 trial in metastatic Castration-Resistant Prostate Cancer (mCRPC) at the Genitourinary Cancers Symposium (ASCO-GU) and followed this with a presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) demonstrating activity of onvansertib in prostate cancer patients showing initial resistance to anti-androgen therapy. We also achieved a critical milestone in our ongoing Phase 1b/2 trial in Acute Myeloid Leukemia (AML), with a complete response (2 CR’s and 1 CRi) to treatment achieved in 3 of 6 (50%) of evaluable patients at the highest doses of onvansertib (27mg/m2 and 40mg/m2) evaluated in combination with standard-of-care chemotherapy, decitabine."

Dr. Adams added, "We achieved a number of key milestones in the first quarter of 2019, including: Successful completion of the first four dose levels, without any dose-limiting toxicities, in the Phase 1b segment of our AML trial; receipt of a "Study May Proceed" notification from the FDA for our Phase 1b/2 trial in metastatic Colorectal Cancer (mCRC) in January and subsequent agreement with PoC Capital to fund this trial."

The Company has advanced its business to-date in 2019, with the following activities and milestone achievements:

Announced Data Demonstrating Significant Synergy of Onvansertib in Combination with Venetoclax in Cell Model of Venetoclax Resistant AML
On April 23, 2019, Trovagene announced preclinical data that provides support for clinical evaluation of onvansertib in combination with venetoclax (Venclexta – AbbVie) in patients with difficult-to-treat relapsed or refractory acute myeloid leukemia (AML). Preclinical data showed that the combination demonstrated synergy (the combined effect of the two drugs is greater than the sum of their individual effects) with a significant decrease in tumor cell viability.

Announced Update to Phase 1b/2 AML Trial Data Presented at AACR (Free AACR Whitepaper) – Additional Patients Achieve Complete Response at Two Highest Dose Levels of Onvansertib
On April 5, 2019, Trovagene announced updates to the Phase1b/2 AML trial data presented at the AACR (Free AACR Whitepaper) conference on April 1, 2019. Complete response (2 CR’s and 1 CRi) to treatment with onvansertib in combination with decitabine was achieved in 3 of 6 (50%) of evaluable patients at the highest doses (27mg/m2 and 40mg/m2). The first complete response was achieved at the highest dose of onvansertib (40mg/m2) in combination with low-dose cytarabine (LDAC). Overall, approximately 90% clinical benefit has been achieved to-date in the trial and there have been no dose limiting toxicities observed. Dose escalation is continuing with enrollment in the onvansertib 60mg/m2 cohort.

Announced Early Data from Phase 2 Trial Indicates Activity of Onvansertib in Prostate Cancer Patients Showing Initial Resistance to Anti-Androgen Therapy
On April 2, 2019, Trovagene announced early data from its ongoing Phase 2 study evaluating onvansertib in combination with Zytiga in patients with mCRPC. Early prostate specific antigen ("PSA") response was observed when onvansertib is added to abiraterone (Zytiga) in 2 of 6 patients to-date; the first patient achieved the primary efficacy endpoint of disease stabilization. The PSA trajectory in the patient achieving the primary efficacy endpoint indicates alteration of the natural history of early signs of resistance to Zytiga. Patients with observed responses to-date harbor the highly aggressive androgen receptor variant (AR-V7) which is known to be resistant to treatment with Zytiga.

Announced Phase 1b/2 Dose Escalation Trial of Onvansertib in Relapsed/Refractory AML Demonstrates Safety, Tolerability and Relative Durability with Complete Responses at Highest Dose Levels
On April 1, 2019, Trovagene announced the presentation of new data from its ongoing Phase 1b/2 study evaluating onvansertib in combination with standard-of-care chemotherapy in AML. The greatest anti-leukemic activity has been observed in the onvansertib + decitabine arm, with complete response in 2 (1 CR and 1 CRi) of 4 (50%) of evaluable patients from the two highest dose levels. There have been no dose-limiting toxicities observed to-date and two-thirds of patients have completed ≥2 cycles of treatment, with 2 patients currently on treatment for more than 11 and 5 months, respectively. There has been a significant association observed between biomarker-positive patients and response to onvansertib treatment.

Announced Presentation Update on Phase 2 Study of Onvansertib in Combination with Zytiga in Patients with mCRPC at ASCO (Free ASCO Whitepaper)-GU
On February 14, 2019, Trovagene announced the presentation of a poster reviewing its ongoing Phase 2 study evaluating onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) at the Genitourinary Cancers Symposium (ASCO-GU) in San Francisco, CA. The data featured demonstrates the safety and tolerability of onvansertib in combination with Zytiga which was confirmed in the safety lead-in portion of the trial that was completed prior to opening the trial to full enrollment. In addition, a second arm is planned with the goal of maximizing clinical activity by reducing the dosing schedule from the current 21-day cycle to a 14-day cycle.

Announced that Trovagene and PoC Capital Entered into an Agreement to Fund Clinical Development of Onvansertib in Metastatic Colorectal Cancer (mCRC)
On January 29, 2019, Trovagene announced an agreement with PoC Capital to fund its Phase 1b/2 trial of onvansertib in combination with FOLFIRI and Avastin in patients with mCRC with a KRAS mutation. Trovagene submitted an Investigational New Drug (IND) application and protocol to the FDA on December 19, 2018, and received a "study may proceed" notification from the FDA, 28-days later, on January 16, 2019. The trial is being conducted at two prestigious cancer centers in the U.S.; USC Norris Comprehensive Cancer Center and The Mayo Clinic.

Announced New Patent Issued for Combination of Onvansertib and Anti-Androgen Drugs to Treat Non-Metastatic and Metastatic Prostate Cancer
On January 23, 2019, Trovagene announced the issuance of a new patent (10,155,006), entitled Combination Therapies and Methods of Use Thereof for Treating Cancer, by the U.S. Patent and Trademark Office (USPTO). This patent broadens previously issued patent (9,566,280), by expanding the use of onvansertib to encompass combination therapies with any anti-androgen and androgen antagonist drug, such as Zytiga, Xtandi and Erleada for the treatment of metastatic and non-metastatic castrate-resistant prostate cancer. The issuance of this patent further strengthens Trovagene’s existing intellectual property portfolio obtained with the licensing of exclusive global development and commercialization rights to onvansertib from Nerviano Medical Sciences in March, 2017.

First Quarter 2019 Financial Results

Total operating expenses were approximately $4.1 million for the three months ended March 31, 2019, a decrease of $0.7 million from $4.8 million for the same period in 2018. The decrease in operating expenses is attributed to a reduction of $1.0 million in SG&A and $0.4 million for cost of revenues related to the disposition of the CLIA lab, and partially offset by an increase of $0.8 million in R&D costs.

Net cash used in operating activities in the first quarter of 2019 was approximately $3.4 million, compared to $2.9 million in the same period in 2018. The year-over-year increase of $0.5 million can be attributed primarily to funding used to advance the onvansertib clinical trials.

Research and development expenses increased by approximately $0.8 million to $2.6 million for the three months ended March 31, 2019 from $1.9 million for the same period in 2018. The overall increase in research and development expenses was primarily due to the increased outside service costs for clinical studies related to the development of our drug candidate, onvansertib. We expect increases in research and development costs as we advance the onvansertib clinical development programs in AML, mCRPC and mCRC.

Selling, general and administrative expenses decreased by approximately $1.0 million to $1.5 million for the three months ended March 31, 2019 from $2.5 million for the same period in 2018. The significant components of the decrease were primarily due to the reduction in salaries and staff costs and stock-based compensation.

The weighted average diluted shares of common stock outstanding used to calculate per share results for the three months ended March 31, 2019 was 4.1 million.

As of March 31, 2019, Trovagene had approximately $11.3 million of cash and cash equivalents

On May 7, 2019 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company developing first-in-class antibody product candidates focused on unmet medical needs in inflammation, reported operating results for the first quarter ended March 31, 2019 and provided pipeline updates (Press release, AnaptysBio, MAY 7, 2019, View Source [SID1234535886]).

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"2019 is set to be an important year for AnaptysBio, with multiple top-line data readouts from our wholly-owned pipeline, initiation of a new Phase 2b trial of etokimab in eosinophilic asthma and submission of an IND for our next development candidate in our wholly-owned pipeline," said Hamza Suria, president and chief executive officer of AnapytsBio. "We look forward to advancing each of these programs as we work to bring novel treatments to patients with severe inflammatory diseases."

Etokimab (ANB020 Anti-IL-33 Program)

In September 2018, the Company reported positive interim top-line data from its Phase 2a proof-of-concept clinical trial of etokimab in adult patients with severe eosinophilic asthma. The Company will present the full data from this trial at the 2019 European Academy of Allergy and Clinical Immunology (EAACI) Congress. AnaptysBio also plans to initiate a multi-dose Phase 2b randomized, double-blinded, placebo-controlled trial of etokimab in eosinophilic asthma in 2019.

The Company is conducting a Phase 2b randomized, double-blinded, placebo-controlled, multi-dose study in 300 adult patients with moderate-to-severe atopic dermatitis, also referred to as the ATLAS trial, to assess different dose levels and dosing frequencies of subcutaneously-administered etokimab, with top-line data expected in the second half of 2019.

AnaptysBio is conducting a randomized, placebo-controlled Phase 2 trial in approximately 100 adult patients with chronic rhinosinusitis with nasal polyps, also referred to as the ECLIPSE trial. Patients are being treated with two multi-dosing frequencies of subcutaneously-administered etokimab or placebo, each in combination with mometasone furoate nasal spray as background therapy. The Company anticipates top-line data from the ECLIPSE trial will be available in the second half of 2019.

ANB019 (Anti-IL-36 Receptor Program)

The Company is conducting a single arm, open-label Phase 2 trial of ANB019 in approximately 10 patients with generalized pustular psoriasis, or GPP, also known as the GALLOP trial, with top-line data expected in mid-2019.

The Company is conducting a randomized, placebo-controlled, multi-dose Phase 2 trial in 50 patients with palmoplantar pustulosis, or PPP, also known as the POPLAR trial, with top-line data anticipated in the first half of 2020.
First Quarter Financial Results

Cash, cash equivalents and investments totaled $484.2 million as of March 31, 2019 compared to $500.2 million as of December 31, 2018, for a decrease of $16.0 million. The decrease primarily relates to cash used for operating activities.

Research and development expenses were $20.6 million for the three months ended March 31, 2019, as compared to $11.8 million for the three months ended March 31, 2018. The increase was primarily due to continued advancement of the Company’s etokimab and ANB019 clinical programs and additional

personnel-related expenses including share-based compensation during the three months ended March 31, 2019.

General and administrative expenses were $4.1 million for the three months ended March 31, 2019, as compared to $3.9 million for the three months ended March 31, 2018. The increase was primarily attributable to additional personnel-related expenses, including share-based compensation.

Net loss was $22.1 million for the three months ended March 31, 2019, or a net loss per share of $0.82, as compared to a net loss of $15.1 million for the three months ended March 31, 2018, or a net loss per share of $0.63.
Financial Guidance
AnaptysBio expects that its cash, cash equivalents and investments will fund its current operating plan at least through the end of 2020.
About Etokimab
Etokimab, previously referred to as ANB020, is an antibody that potently binds and inhibits the activity of interleukin-33, or IL-33, a pro-inflammatory cytokine that multiple studies have indicated is a central mediator of atopic diseases, which AnaptysBio believes is broadly applicable to the treatment of atopic inflammatory disorders, such as atopic dermatitis, eosinophilic asthma, chronic rhinosinusitis with nasal polyps, or CRSwNP, and potentially other allergic conditions. Following completion of a healthy volunteer Phase 1 trial of etokimab, AnaptysBio continued clinical development of etokimab into a Phase 2a trial for moderate-to-severe adult atopic dermatitis and a placebo-controlled Phase 2a trial in severe adult eosinophilic asthma patients. AnaptysBio is conducting its ATLAS trial, a randomized, double-blinded, placebo-controlled multi-dose Phase 2b clinical trial of etokimab in 300 moderate-to-severe adult atopic dermatitis patients where top-line data is anticipated in the second half of 2019. The Company is conducting its ECLIPSE trial, a randomized, double-blinded, placebo-controlled Phase 2 trial of etokimab in approximately 100 adult patients with CRSwNP with top-line data anticipated in the second half of 2019. AnaptysBio also plans to initiate a randomized, double-blinded, placebo-controlled, multi-dose Phase 2b trial of etokimab in patients with eosinophilic asthma in 2019.
About ANB019
ANB019 is an antibody that inhibits the function of the interleukin-36-receptor, or IL-36R, which AnaptysBio plans to initially develop as a potential first-in-class therapy for patients suffering from generalized pustular psoriasis, or GPP, and palmoplantar pustulosis, or PPP. AnaptysBio has previously presented data from this Phase 1 clinical trial, which demonstrated favorable safety, pharmacokinetics and pharmacodynamic properties that supported advancement of ANB019 into Phase 2 studies. AnaptysBio is conducting its GALLOP trial, a Phase 2 study of ANB019 in GPP where top-line data is anticipated in mid-2019, and its POPLAR trial, a Phase 2 study in PPP where top-line data is anticipated in the first half of 2020.

On May 7, 2019 Castle Biosciences, Inc., a skin cancer diagnostics company providing personalized genomic information to improve cancer management decisions, reported two presentations at the 2019 American College of Mohs Surgery (ACMS) Annual Meeting held in Baltimore from May 2-5 (Press release, Castle Biosciences, MAY 7, 2019, View Source [SID1234537263]).

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Progress in the development of a prognostic gene expression profile test in cutaneous squamous cell carcinoma (cSCC) was highlighted in an oral presentation. The total number of deaths from cSCC, one of the most common cancers in the U.S., is approaching or surpassing that from melanoma. Many patients with cSCC will have a favorable prognosis, but 25-40% of high-risk subsets will experience metastasis or develop recurrences. Current cSCC staging systems are evolving but more accurate methods of risk prediction are needed to appropriately direct workup and treatment. The goal of this development program is to identify and validate a clinical test that improves upon existing clinicopathologic staging systems to identify patients who have a high risk for regional/distant metastasis and enable more informed clinical management decisions.

In an ongoing development study, primary cSCC specimens with associated clinical outcome data were accrued from 18 centers. The discovery phase of the program included determining genes identified for their expression in recurrent and non-recurrent tumors. Researchers successfully identified genes that exhibited significant differential expression in cSCC samples from patients who experienced a recurrence, including several specific to regional/distant metastasis. In an archival training cohort of 122 patients, gene expression data from 140 candidate genes were used to identify a preliminary gene set and predictive algorithm.

To assess the predictive value of this assay, Kaplan-Meier survival analysis was performed in an independent validation cohort of 107 patients. Results from the analysis support the predictive value of the test to identify two groups of patients with significantly different risk for regional/distant metastasis (p<0.0001). The positive predictive value of the test in this preliminary validation study was 60%, which compares favorably to the performance of current staging systems in this cohort.

Based on these preliminary validation results, an expanded validation program for the cSCC prognostic test is now underway, including additional archival studies and a prospective validation study.

"The continued progress toward validation of this prognostic test for cSCC demonstrates that improvements in risk identification based on tumor biology are feasible," said Sarah T. Arron, M.D., Ph.D., University of California San Francisco and the San Francisco VA Health System, an investigator in the study. "Clinical use of a validated prognostic test such as this could help inform clinical decisions on staging and adjuvant therapy, and improve upon currently used staging systems."

Second study presented at ACMS

A second study presented as a poster at ACMS highlighted results from a meta-analysis evaluating the performance of the DecisionDx-Melanoma gene expression profile test in four unique, independent patient cohorts.

Results from this meta-analysis with 1,479 patients from four independent cohorts confirm that the DecisionDx-Melanoma test is a significant, independent predictor of recurrence and metastasis in patients with Stage I-III melanoma. Patients identified as highest risk (Class 2B) by the DecisionDx-Melanoma test were 2.9 times more likely to experience recurrence than those identified as lowest risk (Class 1A, p<0.0001), independent of other clinicopathologic features. The meta-analysis, a statistical method considered to be among the highest level of evidence (Level 1A) for prognostic tests, supports the use of the DecisionDx-Melanoma gene expression profile test to inform patient management decisions.

About Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is one of the most common cancers. Approximately 200,000 patients per year are diagnosed with cSCC with high-risk features. Most patients have a favorable prognosis, but a subset of patients will develop metastasis and up to 15,000 patients each year die from their disease. As current staging parameters have a low positive predictive value, many more patients are considered high risk than actually develop metastatic disease. Conversely, many patients who develop metastatic disease are misidentified as low risk. This may lead to over and undertreatment of a substantial number of cSCC patients. To address this clinical need, Castle Biosciences is developing a gene expression profile test designed to improve upon current staging systems and identify patients with cSCC at high risk for metastasis or recurrence, in order to enable more informed clinical decisions regarding adjuvant therapy and other management options.