On August 7, 2019 Transgene (Paris:TNG), a biotech company designing and developing virus-based immunotherapies for the treatment of solid tumors, reported an update on the interim futility analysis of the PHOCUS study of Pexa-Vec in liver cancer (Press release, Transgene, AUG 7, 2019, View Source [SID1234538332]). The independent Data Monitoring Committee (IDMC) of the PHOCUS trial has recommended to stop the study (see press release distributed on August 2, 2019). Transgene is currently analyzing the data of the trial it received from its partner SillaJen, notably in the context of the ongoing Phase 2 clinical trial evaluating the combination regimen of Pexa-Vec and the immunotherapy nivolumab in the same indication. The recommendation to stop the PHOCUS trial is not caused by safety issues of Pexa-Vec.

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Transgene is convinced of the great potential of oncolytic viruses (OV) as this therapeutic class displays numerous advantages that are acknowledged by the scientific and medical community. These include the ability of the viruses to infect and selectively replicate within the tumor, inducing cancer cell destruction, and to elicit a strong immune response against the tumor.

Transgene novel proprietary OV platform Invir.IO allows the arming of these viruses to trigger the expression of anticancer weapons directly in the tumor, thus increasing the efficacy of these molecules while reducing their possible side effects.

The oncolytic viruses derived from the Invir.IO platform have been designed using an optimized strain of Vaccinia Copenhagen. These carry a double deletion TK-RR-, which makes their replication more selective than viruses carrying a simple TK deletion such as Pexa-Vec. In addition, the Invir.IO platform is designed to incorporate several transgenes encoding for a range of specific anticancer weapons which involve well-established immunotherapy mechanisms such as anti-CTLA-4 antibodies.

The collaboration with AstraZeneca was formed on the merits of this platform. As described in the press release distributed on May 2, 2019, Transgene is currently working to design five new oncolytic viruses for AstraZeneca.

Philippe Archinard, PhD, Chairman and CEO of Transgene, commented: "We are obviously disappointed with the outcome of the PHOCUS study; however we remain convinced in the potential of our oncolytic virus pipeline. Our recent collaborative agreement with AstraZeneca highlights the industry interest in the multi-armed OVs that we can generate using our unique Invir.IO platform. We also expect to announce the first clinical data with TG6002 in patients with colorectal cancer later this year. In addition, we expect to announce important clinical results from our most advanced therapeutic vaccines; TG4010 in lung cancer and TG4001 in HPV-Positive head and neck cancer. With funding through to 2022, a clear strategy and novel technology platforms such as Invir.IO and myvac, Transgene is well placed to demonstrate the potential of its novel medicines designed to improve the treatment of solid tumors."

A conference call in English is scheduled on August 7, 2019, at 6:30 p.m. CET (12:30 pm EST).

Webcast link to English language conference call:
https://channel.royalcast.com/webcast/transgene/20190805_1/

Participant telephone numbers:

France: +33 (0) 1 7037 7166

United Kingdom: +44 20 3003 2666

United States: +1 202 204 1514

Confirmation code: Transgene

A replay of the call will be available on the Transgene website (www.transgene.fr) following the live event.

-Ends-

About the PHOCUS trial
The PHOCUS trial was a Phase 3 clinical trial evaluating the oncolytic immunotherapy Pexa-Vec for advanced liver cancer patients who have not received prior systemic treatment for their cancer. The study was conducted by Transgene’s partner, SillaJen.
In the PHOCUS study, patients were randomized to one of two treatment groups: one receiving Pexa-Vec followed by sorafenib and one receiving sorafenib alone. The primary objective of the study was to determine the overall survival of patients treated with Pexa-Vec, followed by sorafenib versus sorafenib alone. Secondary objectives included safety as well as assessments for tumor responses between the two groups as measured by the following endpoints: time to progression, progression-free survival, overall response rate and disease control rate.

About Pexa-Vec
Pexa-Vec (formerly JX-594/TG6006 – pexastimogene devacirepvec) is an oncolytic immunotherapeutic based on an oncolytic vaccinia virus armed with a GM-CSF gene that promotes an anti-tumor immune response. Pexa-Vec is designed to selectively target and destroy cancer cells through three different mechanisms of action: selectively destroy cancer cells through the direct lysis (breakdown) of cancer cells through viral replication, reduce the blood supply to tumors through vascular disruption, and stimulate the body’s immune response against cancer cells.
In a Phase 2 study, results of patients with advanced liver cancer showed that patients receiving the high dose had a statistically significant clinical improvement in terms of overall survival compared to the group receiving the low dose. Median overall survival was respectively 14.1 months in the high-dose group and 6.7 months in the low-dose group, which compares favorably with current approved treatments. (Heo J. et al., Nature Medicine, March 2013, doi: 10.1038/nm.3089)
Transgene has exclusive rights to develop and commercialize Pexa-Vec for the treatment of solid tumors in Europe. Its partner SillaJen, Inc. is focused on developing Pexa-Vec for the North American market and has also granted exclusive development and commercial rights to Pexa-Vec in Hong Kong and The People’s Republic of China to Lee’s Pharmaceutical.

On August 7, 2019 ANI Pharmaceuticals, Inc. ("ANI") (NASDAQ: ANIP) reported its financial results for the three and six months ended June 30, 2019 and reaffirmed its previously issued guidance for adjusted non-GAAP EBITDA and adjusted non-GAAP earnings per share, while updating its 2019 financial guidance for net revenues (Press release, ANI Pharmaceuticals, AUG 7, 2019, View Source [SID1234538349]). The Company will host its earnings conference call this morning, August 7, 2019, at 10:30 AM ET. Investors and other interested parties can join the call by dialing (866) 776-8875. The conference ID is 3823848.

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Financial Summary

(a) See ANI’s Form 10-Q filed August 7, 2019 for discussion of year-to-date results.

(b) See Table 3 for US GAAP reconciliation.

(c) See Table 4 for US GAAP reconciliation.

Arthur S. Przybyl, President and CEO, stated,

"ANI had a strong second quarter, generating net revenues of $54.4 million, an increase of 15% over the prior year period, and record adjusted non-GAAP EBITDA of $23.7 million, an increase of 24% over the prior year period. More importantly, we remain on track to file our supplemental NDA for Cortrophin Gel in the first quarter of 2020.

Generic product revenues increased 20% over the prior year period and we launched one new generic product in late June, Ranitidine capsules. We also received FDA approval for 250 mg/5 ml Vancomycin Oral Solution, which we intend to launch in the third quarter.

During the second quarter, we continued to add to our generic portfolio, through an April distribution agreement with a specialty injectable manufacturer and the June acquisition of seven development stage generic products, which expanded our pipeline of injectable drugs to six."

ANI Updates Guidance for Net Revenues for the Full Year 2019

ANI has updated its full year guidance for net revenues due to the competitive landscape of the Methylphenidate ER market. ANI’s guidance for adjusted non-GAAP EBITDA and adjusted non-GAAP earnings per diluted share remains unchanged from previously issued guidance.

Revised guidance for 2019 net revenues of $220 million to $226 million reflects sales growth of between 9% and 12% over 2018 full year actual results. Previous guidance for net revenues was $231 million to $245 million.

ANI’s estimates are based upon actual results for the six months ending June 30, 2019 and projected results for the remaining six months of the year. ANI’s full year 2019 financial guidance reflects management’s current assumptions regarding customer relationships, product pricing, prescription trends, competition, inventory levels, cost of sales, operating costs, timing of research and development spend, taxes, and the anticipated timing of future product launches and other key events. For the twelve months ending December 31, 2019, ANI is providing guidance on net revenues, adjusted non-GAAP EBITDA, and adjusted non-GAAP diluted earnings per share.

Generic Pharmaceutical Products

Second Quarter Net Revenues – Results and Update

Net revenues from sales of generic pharmaceuticals increased 20% to $36.3 million from $30.2 million in the prior period, primarily due to the launch of Ezetimibe-Simvastatin, Candesartan, and other products launched in 2018 and 2019, as well as increased unit sales of Vancomycin.

Key Generic Pipeline Product

Branded Pharmaceutical Products

Second Quarter Net Revenues – Results and Update

Net revenues from sales of branded pharmaceuticals increased 33% to $14.0 million from $10.5 million in the prior period, primarily due to sales of Arimidex and Casodex, which were launched under ANI’s label in July 2018 and sales of Atacand and Atacand HCT, which were launched under ANI’s label in October 2018. Prior to the launch under the ANI label, net revenues generated by these products was recorded via royalties received and was reported as Royalty and Other.

Key Brand Pipeline Products

Product

Vancocin for Oral Solution Update

ANI is currently advancing a commercialization effort for Vancocin for oral solution. ANI filed a prior approval supplement ("PAS") in September 2018 and it was approved in June 2019. This product will be manufactured at ANI’s site in Baudette, Minnesota and will compete in a market that currently exceeds $450 million annually.

Cortrophin Gel Re-commercialization Update

ANI continues to successfully progress our Cortrophin re-commercialization program. Significant accomplishments since the first quarter 2019 press release (dated May 9, 2019) include:

The completion of a third commercial scale batch of Corticotropin API. This batch was analytically consistent with previously manufactured batches and met all specifications. ANI expects to complete API process validation and registration stability batch manufacturing in the third quarter of 2019.
The initiation of viral clearance studies, which are expected to be completed in the third quarter of 2019.
The manufacture of two commercial scale batches of Cortrophin Gel using commercial scale API. ANI intends to complete the third and final registration batch of drug product in the third quarter of 2019.
ANI remains on track to file a supplemental NDA in the first quarter of 2020.

For further details, please see ANI’s Cortrophin Gel Re-commercialization Milestone Update in Table 5.

Contract Manufacturing

Second Quarter Net Revenues – Results and Update

Contract manufacturing revenues increased 120% to $3.7 million from $1.7 million in the prior year period, primarily due to the impact of contract manufacturing revenues from ANI’s Canadian subsidiary, ANI Pharmaceuticals Canada Inc. ("ANI Canada"), which was acquired in August 2018.

Royalty and Other

Second Quarter Net Revenues – Result and Update

Royalty and other decreased 91% to $0.4 million from $4.9 million, primarily due to the launches of Atacand, Atacand HCT, Arimidex, and Casodex under the ANI label in the second half of 2018. The net revenues from those products are now included in the net sales of branded pharmaceutical products. This decline was tempered by product development and lab services net revenues from ANI Canada.

Key Royalty Product: Yescarta

ANI is entitled to a percentage of global Yescarta net sales as well as a portion of certain product milestones, such as the recent positive opinion issued by the European Medicines Agency ("EMA") Committee for Medicinal Products for Human Use ("CHMP").

Operating Expenses

Operating expenses increased to $45.1 million for the three months ended June 30, 2019, from $40.0 million in the prior year period. The increase was primarily due to a $4.2 million increase in selling, general, and administrative expense as compared with the prior period, as a result of costs related to the new ANI Canada subsidiary, increased U.S.-based headcount and pharmacovigilance compliance costs in continued support of the expansion of our commercial portfolio, higher GDUFA and PDUFA user fees paid to the U.S. FDA, higher legal fees, and increased sales and marketing-related costs. In addition, depreciation and amortization increased by $1.2 million, primarily due to additional amortization expense associated with a March 2019 asset acquisition and a January 2019 royalty buyout payment related to a prior period asset acquisition. These increases were partially offset by a $1.0 million decrease in cost of sales.

Cost of sales as a percentage of net revenues decreased to 29% during the three months ended June 30, 2019, from 35% during same period in 2018. The decrease was primarily due to lower royalty expense resulting from a royalty buy out and lower sales of products under profit-sharing arrangements.

Net Income and Diluted Earnings per Share

Net income was $6.6 million for the three months ended June 30, 2019, as compared to net income of $2.8 million in the prior year period. The effective consolidated tax rate excluding impacts of discrete items for the three months ended June 30, 2019 was 16.8%.

Diluted earnings per share for the three months ended June 30, 2019 was $0.53, based on 12,269 thousand diluted shares outstanding, as compared to diluted earnings per share of $0.23 in the prior year period. Adjusted non-GAAP diluted earnings per share was $1.44, as compared to adjusted non-GAAP diluted earnings per share of $1.13 in the prior year period. For a reconciliation of adjusted non-GAAP diluted earnings per share to the most directly comparable GAAP financial measure, please see Table 4.

ANI Product Development Pipeline

ANI’s pipeline consists of 111 products, addressing a total annual market size of $5.2 billion, based on data from IQVIA. Of these 111 products, 106 were acquired and of these acquired products, ANI expects that at least 56 can be commercialized based on either CBE-30s or prior approval supplements filed with the FDA.

Non-GAAP Financial Measures

The Company’s fiscal 2019 guidance for adjusted non-GAAP EBITDA and adjusted non-GAAP diluted earnings per share is not reconciled to the most comparable GAAP measure. This is due to the inherent difficulty of forecasting the timing or amount of items that would be included in a reconciliation to the most directly comparable forward-looking GAAP financial measures. Because a reconciliation is not available without unreasonable effort, it is not included in this release.

Adjusted non-GAAP EBITDA

ANI’s management considers adjusted non-GAAP EBITDA to be an important financial indicator of ANI’s operating performance, providing investors and analysts with a useful measure of operating results unaffected by non-cash stock-based compensation and differences in capital structures, tax structures, capital investment cycles, ages of related assets, and compensation structures among otherwise comparable companies. Management uses adjusted non-GAAP EBITDA when analyzing Company performance.

Adjusted non-GAAP EBITDA is defined as net income/(loss), excluding tax expense, interest expense, depreciation, amortization, the excess of fair value over cost of acquired inventory, stock-based compensation expense, expense from acquired in-process research and development, gains, losses, and expenses related to the repurchase of convertible debt, expenses related to debt financing, transaction and integration expenses, and other income / expense. Adjusted non-GAAP EBITDA should be considered in addition to, but not in lieu of, net income or loss reported under GAAP. A reconciliation of adjusted non-GAAP EBITDA to the most directly comparable GAAP financial measure is provided in Table 3.

Adjusted non-GAAP Net Income

ANI’s management considers adjusted non-GAAP net income to be an important financial indicator of ANI’s operating performance, providing investors and analysts with a useful measure of operating results unaffected by purchase accounting adjustments, non-cash stock-based compensation, non-cash interest expense, depreciation and amortization, and non-cash impairment charges. Management uses adjusted non-GAAP net income when analyzing Company performance.

Adjusted non-GAAP net income is defined as net income/(loss), plus the excess of fair value over cost of acquired inventory, stock-based compensation expense, transaction and integration expenses, gains, losses, and expenses related to the repurchase of convertible debt, expenses related to debt financing, non-cash interest expense, depreciation and amortization expense, expense from acquired in-process research and development, and non-cash impairment charges, less the tax impact of these adjustments calculated using an estimated statutory tax rate. Management will continually analyze this metric and may include additional adjustments in the calculation in order to provide further understanding of ANI’s results. Adjusted non-GAAP net income should be considered in addition to, but not in lieu of, net income reported under GAAP. A reconciliation of adjusted non-GAAP net income to the most directly comparable GAAP financial measure is provided in Table 4.

Adjusted non-GAAP Diluted Earnings per Share

ANI’s management considers adjusted non-GAAP diluted earnings per share to be an important financial indicator of ANI’s operating performance, providing investors and analysts with a useful measure of operating results unaffected by purchase accounting adjustments, non-cash stock-based compensation, non-cash interest expense, depreciation and amortization, and non-cash impairment charges.

Management uses adjusted non-GAAP diluted earnings per share when analyzing Company
performance.

Adjusted non-GAAP diluted earnings per share is defined as adjusted non-GAAP net income, as defined above, divided by the diluted weighted average shares outstanding during the period, as adjusted for the dilutive effect of the convertible debt notes, when applicable. Management will continually analyze this metric and may include additional adjustments in the calculation in order to provide further understanding of ANI’s results. Adjusted non-GAAP diluted earnings per share should be considered in addition to, but not in lieu of, diluted earnings or loss per share reported under GAAP. A reconciliation of adjusted non-GAAP diluted earnings per share to the most directly comparable GAAP financial measure is provided in Table 4.

On August 7, 2019 AstraZeneca and MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada) reported positive results from the Phase III PROfound trial of Lynparza (olaparib) in men with metastatic castration-resistant prostate cancer (mCRPC) who have a *homologous recombination repair gene mutation (HRRm) and have progressed on prior treatment with new hormonal anticancer treatments (e.g. enzalutamide and abiraterone) (Press release, AstraZeneca, AUG 7, 2019, View Source [SID1234538256]).

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Results from the trial showed a statistically-significant and clinically-meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS) with Lynparza vs. enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or ATM gene mutations, a subpopulation of HRR gene mutations. The safety and tolerability profile of Lynparza was generally consistent with previous trials.

José Baselga, Executive Vice President, Oncology R&D, said: "For men with metastatic castration-resistant prostate cancer the disease remains deadly, especially in those who have failed on a new hormonal anticancer treatment. This trial is the only positive Phase III trial of any PARP inhibitor in metastatic castration-resistant prostate cancer, where the need for new, effective therapies is high. The PROfound trial also demonstrates the potential value of genomic testing in this at-risk patient population. We look forward to discussing these results with global health authorities soon."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "Metastatic castration-resistant prostate cancer is a deadly disease and represents an area of critical unmet medical need. The Phase III PROfound trial is another example of MSD and AstraZeneca’s shared commitment to improving long-term outcomes for people living with cancer. These results represent the potential for a new, oral targeted treatment option for this patient population."

AstraZeneca and MSD plan to present the full data from the trial at a forthcoming medical meeting. The companies are also exploring additional trials in prostate cancer, including the ongoing Phase III PROpel trial, testing Lynparza as a 1st-line therapy in mCRPC, in combination with abiraterone.

About PROfound

PROfound is a prospective, multicentre, randomised, open-label, Phase III trial testing the efficacy and safety of Lynparza versus enzalutamide or abiraterone in patients with mCRPC who have progressed on prior treatment with new hormonal anticancer treatments and have a qualifying tumour mutation in one of 15 genes involved in the HRR pathway, including among them BRCA1/2, ATM and CDK12.

About metastatic castration-resistant prostate cancer

Prostate cancer is the second-most common cancer in men, with an estimated 1.3 million new cases diagnosed worldwide in 2018 and is associated with a significant mortality rate.1 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.2 mCRPC occurs when prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.2 Approximately 10-20% of men with advanced prostate cancer will develop CRPC within five years, and at least 84% of these will have metastases at the time of CRPC diagnosis.3 Of men with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.3 Despite an increase in the number of available therapies for men with mCRPC, five-year survival remains low.3

About Lynparza

Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2. Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death. Lynparza is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR pathway.

Lynparza is currently approved in 64 countries, including those in the EU, for the maintenance treatment of platinum-sensitive relapsed ovarian cancer regardless of BRCA status. It is approved in the US, EU, Japan and several other countries as 1st-line maintenance treatment of BRCAm advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 40 countries, including the US and Japan, for germline BRCAm HER2-negative metastatic breast cancer previously treated with chemotherapy; in the EU this includes locally advanced breast cancer. Regulatory reviews are underway in other jurisdictions for ovarian, breast and pancreatic cancers.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, is approved for advanced ovarian cancer and metastatic breast cancer and has been used in over 25,000 patients worldwide. Lynparza has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

In January 2016, AstraZeneca announced that Lynparza was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) for the monotherapy treatment of BRCA1/2- or ATM gene-mutated mCRPC in patients who have received a prior taxane-based chemotherapy and at least one newer hormonal agent (abiraterone or enzalutamide), based on the positive results of the TOPARP-A Phase II trial.

About the AstraZeneca and MSD strategic oncology collaboration

In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the United States and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and potential new medicine selumetinib, a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and selumetinib in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance Oncology as one of AstraZeneca’s four Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by our investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.

On August 7, 2019 Kezar Life Sciences, Inc. (Nasdaq: KZR), a clinical-stage biotechnology company discovering and developing novel small molecule therapeutics to treat unmet needs in autoimmunity and cancer, reported its second quarter 2019 financial results and corporate highlights (Press release, Kezar Life Sciences, AUG 7, 2019, View Source [SID1234538299]).

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"I’m proud of the tremendous progress made by the team over the quarter, culminating with the first-in-patient data reported with KZR-616," said John Fowler, Chief Executive Officer. "The broad therapeutic potential demonstrated thus far by KZR-616 reinforces our view that selective immunoproteasome inhibition can target multiple autoimmune diseases. To that end, in addition to having initiated the Phase 2 portion of the MISSION study in lupus nephritis patients, we are pleased to announce that the Phase 2 PRESIDIO and MARINA trials have commenced in four additional autoimmune indications—dermatomyositis, polymyositis, autoimmune hemolytic anemia, and immune thrombocytopenia. Furthermore, we remain on-track to nominate the first oncology clinical candidate from our novel protein secretion program before the end of the year."

Recent Clinical and Business Highlights

KZR-616 (Selective Immunoproteasome Inhibitor)

MISSION Study

The Phase 1b/2 MISSION study in systemic lupus erythematosus (SLE) patients with and without nephritis is currently ongoing.

We reported promising data with KZR-616 in patients with SLE at the European League Against Rheumatism (EULAR) 2019 Annual Meeting. Initial data were reported from 3 cohorts of the open-label dose escalation portion of the trial (Phase 1b). The study met its objectives by establishing the safety and tolerability of KZR-616 and identifying doses to advance into our Phase 2 clinical trials.

Enrollment to the Phase 1b portion of the MISSION study is ongoing and updated data from cohorts testing step-up dosing to a 60 mg dose are expected in Q4 2019.

The Phase 2 portion of the MISSION study, which is evaluating KZR-616 for the treatment of lupus nephritis (LN), was initiated.

PRESIDIO Study

We recently initiated the PRESIDIO study (NCT04033926). This is a Phase 2 randomized, double-blind, placebo-controlled, crossover, multicenter study to evaluate the safety, tolerability, efficacy, PK and PD of treatment with KZR-616 in patients with active dermatomyositis (DM) or polymyositis (PM). The trial is expected to enroll 24 patients with either DM or PM.

MARINA Study

We recently initiated the MARINA study (NCT04039477). MARINA is a Phase 2 randomized, dose-blind, multicenter study to evaluate the safety and efficacy of KZR-616 in the treatment of patients with autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). The trial is expected to enroll 40 patients with either AIHA or ITP.

Protein Secretion Program (Sec61 translocon modulation)

Our research and discovery efforts targeting the protein secretion pathway as a potential therapy for oncology indications is progressing well, and we remain on track to nominate a first clinical candidate before the end of the year.

Management Update

Kezar announced today that Niti Goel, MD, Chief Medical Officer, will be departing the company following a transition period ending October 1, 2019.

"On behalf of the Executive Team and Board of Directors, I would like to sincerely thank Niti for her contributions during her tenure at Kezar," said John Fowler, Chief Executive Officer. "Niti’s exceptional skill designing innovative clinical trials and her unwavering commitment to patients has positioned KZR-616 for success in our Phase 2 studies and will be missed."

Financial Results

Cash, cash equivalents and marketable securities totaled $93.4 million as of June 30, 2019, compared to $107.4 million as of December 31, 2018. The decrease in cash, cash equivalents and marketable securities was primarily attributable to cash used by the company in operations to advance its clinical stage programs as well as preclinical research and development.

Research and development expenses for the second quarter of 2019 increased by $1.7 million to $6.9 million from $5.2 million in the second quarter of 2018. This increase was primarily related to advancing both the KZR-616 clinical program across indications and the protein secretion preclinical program.

General and administrative expenses for the second quarter of 2019 increased by $0.7 million to $2.4 million from $1.7 million in the second quarter of 2018. The increase was primarily due to an increase in personnel expenses and costs related to operating as a public company.

Net loss for the second quarter of 2019 was $8.7 million, or $0.46 per basic and diluted common share, compared to a net loss of $6.8 million, or $3.31 per basic and diluted common share, for the second quarter of 2018.

Total shares outstanding were 19.1 million as of June 30, 2019. Additionally, there were outstanding options to purchase 2.9 million shares of common stock at a $8.02 weighted average exercise price as of June 30, 2019.

About KZR-616

KZR-616 is a novel, first-in-class, selective immunoproteasome inhibitor with broad therapeutic potential across multiple autoimmune diseases. Nonclinical research demonstrates that selective immunoproteasome inhibition results in a broad anti-inflammatory response in animal models of several autoimmune diseases, while avoiding immunosuppression. Phase 1a clinical trial results in healthy volunteers provide evidence that KZR-616 potentially avoids adverse effects caused by currently marketed non-selective proteasome inhibitors, which we believe prevent them from being utilized as a chronic treatment in autoimmune disorders. Phase 2 trials have commenced for the treatment of lupus nephritis (MISSION study), dermatomyositis and polymyositis (PRESIDIO study), and autoimmune hemolytic anemia and immune thrombocytopenia (MARINA study).

About Protein Secretion

We are conducting research and discovery efforts targeting protein secretion pathways as potential therapies for oncology and immuno-oncology indications. In mammalian cells, the secretion of proteins such as cytokines and the expression of cell surface transmembrane proteins such as cytokine receptors involve a process called cotranslational translocation. For most proteins, this process occurs via the Sec61 translocon, a highly conserved multi-subunit protein complex found in the membrane of the endoplasmic reticulum of all cells. Inhibition of the Sec61 translocon with small molecules blocks the secretion of some or all proteins, which can result in several physiologic outcomes, including altered cellular function, inhibition of cytokine release and/or cell death. We believe this platform has the potential to yield oral small molecule alternatives to currently marketed biologic therapeutics, to act as cytotoxic anti-cancer agents or to block the secretion of novel targets of interest in immuno-oncology or inflammation.

On August 7, 2019 Cambrex Corporation (NYSE: CBM), the leading small molecule company providing drug substance, drug product and analytical services across the entire drug lifecycle, reported that it will not hold a second quarter 2019 earnings conference call and will not update previously provided financial guidance given the pending acquisition by an affiliate of the Permira funds (Press release, Cambrex, AUG 7, 2019, View Source [SID1234538333]).

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

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