On November 5, 2019 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs, reported that it will report its third quarter 2019 financial and operating results on Tuesday, November 12, 2019, following the close of the U.S. financial markets (Press release, Lineage Cell Therapeutics, NOV 5, 2019, View Source [SID1234550332]). Lineage management will also host a conference call and webcast on Tuesday, November 12, 2019, at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss its third quarter 2019 financial results and to provide a business update.

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

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

                  Schedule Your 30 min Free Demo!

Interested parties may access the conference call by dialing (866) 888-8633 from the U.S. and Canada and (636) 812-6629 from elsewhere outside the U.S. and Canada and should request the "Lineage Cell Therapeutics Call". A live webcast of the conference call will be available online in the Investors section of Lineage’s website. A replay of the webcast will be available on Lineage’s website for 30 days and a telephone replay will be available through November 19, 2019, by dialing (855) 859-2056 from the U.S. and Canada and (404) 537-3406 from elsewhere outside the U.S. and Canada and entering conference ID number 1473397.

On November 5, 2019 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported financial results for the three and nine months ended September 30, 2019 and provided an operating forecast and program updates (Press release, Ligand, NOV 5, 2019, View Source [SID1234550331]). Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time to discuss this announcement and answer questions.

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

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

                  Schedule Your 30 min Free Demo!

"We are very pleased with how the company is performing as we approach the end of the year," said John Higgins, Chief Executive Officer of Ligand. "In the past quarter we had new products and market launches from our partnered portfolio that we expect to drive increased royalties. Substantial new data were announced for late-stage or marketed products that hold the promise for further revenue growth. In addition, we acquired a company to further expand our antibody discovery business and closed new licensing deals, adding to our large partner portfolio. Financially, the business is strong in regards to both the balance sheet and the financial growth outlook. We are doing well as a company and are pleased to expand our Board last month with the addition of Sarah Boyce, a talented and accomplished biotech executive."

Third Quarter 2019 Financial Results

Total revenues for the third quarter of 2019 were $24.8 million, compared with $45.7 million for the same period in 2018. Royalties in the third quarter of 2019 were $9.8 million and primarily consisted of royalties from Kyprolis and EVOMELA. Royalties in the third quarter of 2018 were $36.1 million and included royalties from Promacta, which was sold to Royalty Pharma as of March 6, 2019, for $827 million; Ligand did not receive any Promacta royalties in the third quarter of 2019 and will not receive any Promacta royalties going forward. Material sales were $6.8 million for the third quarter of 2019, compared with $7.0 million for the same period in 2018. License fees, milestones and other revenues were $8.2 million for the third quarter of 2019, compared with $2.5 million for the same period in 2018.

Cost of material sales was $3.1 million for the third quarter of 2019, compared with $1.5 million for the same period in 2018, with higher costs due to the mix of Captisol sales. Amortization of intangibles was $3.6 million for the third quarter of 2019, compared with $5.7 million for the same period in 2018. Research and development expense was $13.7 million for the third quarter of 2019, compared with $5.5 million for the same period of 2018, with the increase due to costs associated with the Vernalis Design Platform ("VDP") research team and non-cash amortization of the upfront investments in the Palvella and Novan programs. General and administrative expense was $9.5 million, compared with $9.6 million for the same period in 2018.

Net loss for the third quarter of 2019 was $15.3 million, or $0.81 per diluted share, compared with net income of $67.4 million, or $2.80 per diluted share, for the same period in 2018. The third quarter of 2019 net loss was affected by a non-cash change in the value of Ligand’s investments of $10.5 million, while the third quarter of 2018 net income was affected by a net non-cash $59.3 million gain from the value of Ligand’s investments. Adjusted net income for the third quarter of 2019 was $9.5 million, or $0.49 per diluted share, compared with $31.7 million, or $1.32 per diluted share, for the same period in 2018. The third quarter 2019 adjusted diluted EPS was impacted by a change in tax assumptions resulting in a reduction of EPS by $0.12 in the quarter. Please see the table below for a reconciliation of net loss to adjusted net income.

As of September 30, 2019, Ligand had cash, cash equivalents and short-term investments of $1.1 billion. Cash used for share repurchases in the third quarter of 2019 was approximately $181.2 million, which repurchased approximately 1.8 million shares.

Year-to-Date Financial Results

Total revenues for the nine months ended September 30, 2019 were $93.3 million, compared with $191.9 million for the same period in 2018. Royalties in the nine months ended September 30, 2019 were $35.9 million, compared with $88.3 million for the nine months ended September 30, 2018. Royalties for the nine months ended September 30, 2019 primarily consisted of royalties from Promacta, Kyprolis and EVOMELA and do not include contribution from Promacta after March 6, 2019, whereas 2018 royalties included a full nine months of Promacta royalties. Material sales were $24.4 million, compared with $19.0 million for the same period in 2018, with the change due to the timing of Captisol purchases for use in clinical trials and commercial products. License fees, milestones and other revenues were $33.0 million, compared with $84.5 million for the same period in 2018, which included a $47 million payment from WuXi Biologics to amend its OmniAb platform license agreement as well as a $20 million upfront payment upon the licensing of Ligand’s GRA program.

Cost of material sales was $9.4 million for the nine months ended September 30, 2019, compared with $3.4 million for the same period in 2018, with the change due to higher sales and mix of Captisol sales in 2019. Amortization of intangibles was $10.6 million, compared with $12.3 million for the same period in 2018. Research and development expense was $37.2 million, compared with $19.0 million for the same period of 2018, with the increase due to costs associated with recent acquisitions. General and administrative expense was $31.6 million, compared with $26.6 million for the same period in 2018, with the increase due to costs associated with recent acquisitions and non-cash stock-based compensation expense.

Net income for the nine months ended September 30, 2019 was $636.7 million, or $31.29 per diluted share, compared with $185.8 million, or $7.61 per diluted share, for the same period in 2018. Net income for the nine months ended September 30, 2019 was impacted by an after-tax gain of approximately $643 million on the sale of Ligand’s Promacta license to Royalty Pharma. Adjusted net income from continuing operations for the nine months ended September 30, 2019 was $48.2 million, or $2.37 per diluted share after taking into account the tax changes primarily related to Promacta, compared with $127.9 million, or $5.44 per diluted share, for the same period in 2018. Please see the table below for a reconciliation of net income to adjusted net income.

2019 Financial Guidance

Ligand is affirming its revenue guidance for 2019 with total revenues expected to be approximately $118 million. Revenues, cost of goods and operating expenses are all performing in line with expectations and guidance. Ligand is updating its guidance for adjusted diluted EPS to $3.00 per share from $3.20 per share previously to account for changes in tax expense allocated to adjusted EPS compared with initial estimates, primarily related to the $827 million sale of the Promacta royalty earlier this year.

Third Quarter 2019 and Recent Business Highlights

OmniAb Platform Updates

Acquisition and New Licenses

Ligand acquired Ab Initio Biotherapeutics for $12 million. Ab Initio has a patented antigen technology that is synergistic with the OmniAb therapeutic antibody discovery platform, providing Ligand’s current and potential new partners enhanced capabilities for the discovery of therapeutic antibodies against difficult-to-access cellular targets. Ab Initio has a collaboration agreement with Pfizer to discover novel therapeutic antibodies against an undisclosed target in the G-protein coupled receptor superfamily.
Ligand entered into new OmniAb license agreements with Takeda, GigaGen, Talem Therapeutics, Kira Pharma and AbVivo.
Select OmniAb Partner Updates

CStone Pharmaceuticals released pooled safety data from the Phase 1b (GEMSTONE-101) study of their anti-PD-L1 antibody CS1001 in a poster presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress, demonstrating the promising safety and tolerability profile of CS1001.
CStone Pharmaceuticals announced results from the esophageal squamous cell carcinoma cohort of a Phase 1b clinical trial of CS1001 in an oral presentation at the 22nd Annual Meeting of the Chinese Society of Clinical Oncology.
Recent OmniAb Publications

A paper by Ligand scientists entitled "Discovery of high affinity, pan-allelic, and pan-mammalian reactive antibodies against the myeloid checkpoint receptor SIRPα" was published in the journal mAbs.
Other Licensing and Acquisition Events

Ligand entered a license and supply agreement with SQ Innovation AG for use of Ligand’s Captisol technology in the formulation of high-concentration furosemide for the treatment of edema in patients with heart failure. Ligand is eligible to receive potential milestone payments and royalties, as well as revenue from Captisol materials sales.
Ligand entered into new Captisol clinical use or license and supply agreements with Millennium/Takeda, BendaRx Corporation, Hikma, the University of Edinburgh and Quadria Bio.
Additional Pipeline and Partner Developments

Kyprolis third quarter sales totaled $280 million, consisting of Amgen-reported October 29, 2019 Q3 sales of Kyprolis of $266 million and Ono Pharmaceutical Co.-reported October 30, 2019 Q3 sales of Kyprolis in Japan of $14 million.
On September 13, 2019 Amgen announced the Phase 3 CANDOR study evaluating Kyprolis in combination with dexamethasone and Darzalex compared to Kyprolis and dexamethasone alone met its primary endpoint of progression-free survival. The regimen resulted in a 37% reduction in the risk of progression or death in patients with relapsed or refractory multiple myeloma treated with KdD and the median PFS for patients treated with Kd alone was 15.8 months.
Amgen announced on October 31 that it has entered into a strategic collaboration with BeiGene to expand its oncology presence in China. BeiGene is an oncology-focused biotechnology company with an established commercial and clinical development organization in China. Under the agreement, BeiGene will commercialize Kyprolis in China over the next 5 to 7 years along with two other oncology products, Xgeva and Blincyto. Amgen and BeiGene will share the profits and losses equally. Kyprolis is currently in a Phase 3 trial in China.
CASI Pharmaceuticals launched Evomela in China; Evomela uses Ligand’s Captisol technology in its formulation.
Retrophin announced that it will present new data from the Phase 2 DUET Study examining the impact of sparsentan on quality of life in focal segmental glomerulosclerosis at the American Society of Nephrology (ASN) Kidney Week 2019.
Novan completed patient recruitment in the B-SIMPLE (Berdazimer Sodium In Molluscum Patients with Lesions) Phase 3 pivotal trials with SB206 for the treatment of molluscum contagiosum. Novan affirmed that topline data from these trials are expected in the first quarter of 2020.
Sage Therapeutics launched Zulresso (brexanolone) injection. With this launch, Zulresso is the 11th FDA-approved drug to use Ligand’s Captisol technology.
Sermonix Pharmaceuticals announced enrollment and dosing of the first patient into a Phase 2 clinical trial of its lead investigational drug, lasofoxifene, and announced completion of a $26 million financing to fund the trial through to completion.
Verona Pharma presented data from a Phase 2b trial with nebulized ensifentrine in chronic obstructive pulmonary disease (COPD) at the CHEST Annual Meeting and presented data from a Phase 2 trial with its dry powder inhaler formulation of ensifentrine in COPD at the European Respiratory Society International Congress.
Marinus Pharmaceuticals announced that results from its Phase 2 trial of ganaxolone in Refractory Status Epilepticus (RSE) were presented at the Neurocritical Care Society 17th Annual Meeting in Vancouver, BC. Ganaxolone met the primary endpoint in the study with none of the 17 patients progressing to IV anesthetics within 24 hours of treatment initiation.
In September, results of a randomized Phase 2 study of M6620, an ATR kinase inhibitor in development by Merck KGaA formulated using Captisol, were presented at ESMO (Free ESMO Whitepaper) 2019 demonstrating that the addition of M6620 to gemcitabine extended PFS without additional toxicity in patients with platinum-resistant, high-grade serous ovarian cancer.
Takeda Pharmaceutical announced results of a Phase 1 clinical proof-of-concept study of Captisol-enabled TAK-925, a selective orexin type-2 receptor (OX2R) agonist, in individuals with narcolepsy type 1.
Opthea announced positive Phase 2b results demonstrating that OPT-302 combination therapy met the primary endpoint of superiority in mean visual acuity gain at 24 weeks compared to Lucentis monotherapy in treatment-naïve patients with wet age-related macular degeneration; these data were presented at the European Society of Retina Specialists 2019 Congress.
Nucorion Pharmaceuticals closed a $5 million Series B financing to support the Phase 1 clinical development in the U.S. for its lead program, NCO-1010, for the treatment of hepatitis B; NCO-1010 utilizes Ligand’s LTP Platform technology.
Internal R&D

Ligand announced positive topline results from a Phase 1 clinical trial of its internal Captisol-enabled Iohexol program. Clinical data will be presented at ASN Kidney Week 2019 in Washington, DC on November 8th, 2019 and the 2019 Contrast Media Research Symposium in Erice, Italy on November 11th, 2019.
Corporate Events

Ligand announced the appointment of Sarah Boyce to the Company’s Board of Directors, increasing the total number of Ligand directors to nine. Ms. Boyce brings a breadth of commercial and business development experience that will be valuable as the Company builds its portfolio of tools and drug discovery technologies to help serve the pharmaceutical industry.
Adjusted Financial Measures

The Company reports adjusted net income and adjusted net income per diluted share in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The Company’s financial measures under GAAP include stock-based compensation expense, amortization of debt-related costs, amortization related to acquisitions and intangible assets, changes in contingent liabilities, mark-to-market adjustments for amounts relating to its equity investments in public companies, excess tax benefit from share-based compensation, unissued shares relating to its Senior Convertible Notes, gain on the sale of Promacta and others that are listed in the itemized reconciliations between GAAP and adjusted financial measures included at the end of this press release. However, other than with respect to total revenues, the Company only provides financial guidance on an adjusted basis and does not provide reconciliations of such forward-looking adjusted measures to GAAP due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation, including adjustments that could be made for changes in contingent liabilities, changes in the market value of its investments in public companies, stock-based compensation expense and effects of any discrete income tax items. Management has excluded the effects of these items in its adjusted measures to assist investors in analyzing and assessing the Company’s past and future core operating performance. Additionally, adjusted earnings per diluted share is a key component of the financial metrics utilized by the Company’s board of directors to measure, in part, management’s performance and determine significant elements of management’s compensation.

Conference Call

Ligand management will host a conference call today beginning at 4:30 p.m. Eastern time (1:30 p.m. Pacific time) to discuss this announcement and answer questions. To participate via telephone, please dial (833) 591-4752 from the U.S. or (720) 405-1612 from outside the U.S., using the conference ID 6093759. To participate via live or replay webcast, a link is available at www.ligand.com.

On November 5, 2019 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported third quarter 2019 financial results and provided a corporate update (Press release, Kura Oncology, NOV 5, 2019, View Source [SID1234550330]).

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

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

                  Schedule Your 30 min Free Demo!

"We continue to be very encouraged by our growing body of data that support the potential of tipifarnib, highlighted recently by impressive results from our ongoing Phase 2 trial in HRAS mutant head and neck squamous cell carcinomas (HNSCC)," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "These data underscore the activity of tipifarnib in this difficult-to-treat patient population, and we believe they increase the probability of success of our registrational strategy in HRAS mutant HNSCC. We continue to execute on our AIM-HN registration-directed trial, which, if positive, will establish tipifarnib as a first-in-class farnesyl transferase inhibitor for patients with cancer. In addition, we look forward to additional data later this year from our ongoing Phase 2 trial in angioimmunoblastic T-cell lymphoma (AITL), an indication for which we are seeking regulatory feedback regarding next steps."

"Meanwhile, we continue to make steady and encouraging progress with our emerging pipeline programs," Dr. Wilson continued, "including continued dose escalation of our ERK inhibitor, KO-947, and the initiation of a Phase 1 trial of our first-in-class menin-MLL inhibitor, KO-539, in patients with relapsed or refractory acute myeloid leukemia (AML). We believe both of our early-stage drug candidates represent differentiated approaches that could potentially address large indications with high unmet need, and we look forward to sharing updates on all of our progress in the months ahead."

Recent Highlights

Durable anti-tumor activity in Phase 2 trial of tipifarnib in HRAS mutant HNSCC – Last week, Kura reported updated data from its RUN-HN Phase 2 trial of tipifarnib in HNSCC patients with high HRAS mutant variant allele frequency at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston. The preliminary results showed that 10 of the 18 efficacy-evaluable patients achieved a confirmed partial response (PR), for an objective response rate of 56%. In addition, eight patients experienced disease stabilization, including two who achieved an unconfirmed PR, one of whom was awaiting a confirmatory response assessment as of the data cutoff date. The median progression-free survival (PFS) of the 18 evaluable patients treated with tipifarnib was 6.1 months, compared to 2.8 months on their last prior therapy, including 8.3 months among patients who achieved a PR on tipifarnib and 4.5 months for those with stable disease. Patients had a median of two prior lines of therapy (range 0-6), with no responses observed on their last prior therapy.

Updated Phase 2 data support enrichment strategy in ongoing registration-directed trial – Of the eight efficacy-evaluable patients in the RUN-HN Phase 2 trial who were prospectively enrolled with high HRAS mutant variant allele frequency, three achieved a confirmed PR and five had stable disease, including two who achieved an unconfirmed PR, one of whom is awaiting a confirmatory response assessment. Kura’s registration-directed trial, AIM-HN, is designed to enroll at least 59 evaluable HNSCC patients with high HRAS mutant variant allele frequency who have received prior platinum-based therapy. AIM-HN was initiated in November 2018 and is now open in more than 75 clinical sites worldwide. The trial is expected to require approximately two years for full enrollment. Based upon the statistical assumptions, AIM-HN could be positive as soon as 15 responses are confirmed.

Positive Phase 2 trial of tipifarnib in HRAS mutant urothelial carcinoma – In September 2019, Kura reported that an investigator-sponsored Phase 2 trial of tipifarnib in HRAS mutant urothelial carcinomas met its primary efficacy endpoint prior to completion of enrollment. The trial is being conducted at the Samsung Medical Center in Seoul, South Korea. Five of the 13 evaluable patients experienced confirmed objective responses, with four patients having experienced PFS of greater than 6 months. Further analyses of the trial are ongoing, and data are expected to be presented at a medical meeting next year.

Data from Phase 2 trial of tipifarnib in AITL accepted for oral presentation at ASH (Free ASH Whitepaper). In June 2019, Kura announced that the primary endpoint was achieved in both expansion cohorts in its Phase 2 trial of tipifarnib in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Additional data, including new patients from the AITL expansion cohort, have been accepted for oral presentation at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2019.

Expanded patent exclusivity for tipifarnib – In September 2019, the U.S. Patent and Trademark Office issued a new patent further extending Kura’s exclusivity to the use of any farnesyl transferase inhibitor (FTi) for the treatment of CXCL12-expressing PTCL and AML. This adds to the Company’s growing portfolio of patents involving CXCL12 pathway biomarkers and follows the issuance of another patent earlier this year that covers the use of any FTi for the treatment of HRAS mutant HNSCC. These new patents expire in 2037 and 2036, respectively, excluding any possible patent term extension. The Company continues to aggressively pursue additional intellectual property protection, both in the U.S. and abroad.

Initiated Phase 1 trial of KO-539 in relapsed or refractory AML – In September 2019, the first patient was dosed in a Phase 1 trial of KO-539, Kura’s first-in-class, potent and selective small molecule inhibitor of the menin-mixed lineage leukemia (menin-MLL) interaction. The Phase 1, open-label, dose-escalation trial is designed to determine the recommended Phase 2 dose or maximum tolerated dose of KO-539 in patients with relapsed or refractory AML. Upon completion of the dose-escalation portion of the trial, expansion cohorts are planned to further assess the safety and activity of KO-539 in specific genetic subgroups, such as patients with MLL fusions or partial tandem duplications and patients with mutations in the NPM1 oncogene.

Strengthened senior leadership team and board of directors – Kura recently added Kathleen Ford as Chief Operating Officer, James Basta as Chief Legal Officer and Diane Parks as a member of the board of directors. Previously, Ms. Ford was Senior Vice President, Head of Global Clinical Operations at Merck Serono, a division of Merck KGaA, Mr. Basta was Senior Vice President, Chief Corporation Counsel at Biogen, and Ms. Parks was most recently Senior Vice President, Head of U.S. Commercial at Kite Pharma. All three are valuable additions to Kura, as the Company continues to advance its three clinical-stage oncology assets and begins to focus on commercial readiness.
Financial Results

Research and development expenses for the third quarter of 2019 were $12.5 million, compared to $11.7 million for the third quarter of 2018.

General and administrative expenses for the third quarter of 2019 were $5.1 million, compared to $4.3 million for the third quarter of 2018.

Net loss for the third quarter of 2019 was $16.4 million, or $0.36 per share, compared to $15.0 million, or $0.40 per share, for the third quarter of 2018.

Cash, cash equivalents and short-term investments totaled $250.1 million as of September 30, 2019, compared with $179.0 million as of December 31, 2018.

Management continues to expect that current cash, cash equivalents and short-term investments will be sufficient to fund current operations into the second half of 2021.
Upcoming Milestones

Additional data from the AITL expansion cohort in the ongoing Phase 2 trial of tipifarnib in PTCL at ASH (Free ASH Whitepaper) in December 2019

Regulatory feedback from the Phase 2 trial of tipifarnib in AITL in the first half of 2020

Additional data from the ongoing Phase 2 trial of tipifarnib in chronic myelomonocytic leukemia (CMML) in the first half of 2020

Initiation of a proof-of-concept study of tipifarnib in pancreatic cancer in 2020

Data from the Phase 2 investigator-sponsored trial of tipifarnib in urothelial carcinoma in 2020

Potential for full enrollment in the AIM-HN registration-directed trial of tipifarnib in HRAS mutant HNSCC by the end of 2020

Completion of the dose-escalation portion of the Phase 1 trial of KO-947 by the end of 2019 or early 2020

Initiation of tumor-specific extension cohort(s) in the Phase 1 trial of KO-947 in 2020

Achievement of a recommended Phase 2 dose in the Phase 1 dose-escalation trial of KO-539 in 2020
Conference Call and Webcast

Kura’s management will host a webcast and conference call today at 4:30 p.m. ET / 1:30 p.m. PT, November 5, 2019, to discuss the financial results for the third quarter 2019 and provide a corporate update. The live call may be accessed by dialing (877) 516-3514 for domestic callers and (281) 973-6129 for international callers and entering the conference code: 5159117. A live webcast of the call will be available from the Investors and Media section of the Company’s website at www.kuraoncology.com, and a replay will be available shortly after the live event.

On November 5, 2019 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported presentations on two ongoing clinical programs, JTX-4014 and vopratelimab, at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 34th Annual Meeting, being held November 6-10, 2019 in National Harbor, Maryland (Press release, Jounce Therapeutics, NOV 5, 2019, View Source [SID1234550329]).

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

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

                  Schedule Your 30 min Free Demo!

"Our poster sessions at this year’s SITC (Free SITC Whitepaper) conference demonstrate the progress we have made to date on both of our clinical-stage programs, vopratelimab, an ICOS agonist, and JTX-4014, a PD-1 inhibitor. We have previously shown the relationship between the vopratelimab-associated emergence of ICOS hi CD4 T cells and clinical benefit," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "The EMERGE trial builds on the biology of induction of ICOS hi CD4 T cells by ipilimumab and their expansion and sustained activation by vopratelimab. We will provide the scientific rationale for the unique dosing and sequencing strategy of ipilimumab and vopratelimab in EMERGE, which we believe optimizes ICOS hi CD4 T cell priming and agonist biology. In a separate poster at SITC (Free SITC Whitepaper), the safety and preliminary efficacy data for JTX-4014 being presented supports the use of this PD-1 inhibitor in combination with our other product candidates."

Poster Presentation Details:

Title: Phase 1 First in Human Study of Programmed Cell Death Receptor-1(PD-1) Inhibitor Monoclonal Antibody (mAb) JTX-4014 in Adult Subjects with Advanced Refractory Solid Tumor Malignancies
Presentation Date and Time: Friday, November 8, 2019, 7:00am – 8:00pm ET
Presenter: Kyriakos P. Papadopoulos, M.D.
Abstract ID: P439

Jounce researchers describe the safety, preliminary efficacy and recommended Phase 2 doses for JTX-4014 including:

Acceptable safety profile for JTX-4014 based on a 6-cohort dose-escalation trial. There were no deaths or dose limiting toxicities, few Grade 3/4 adverse events and the only related serious adverse event (SAE) was pneumonitis, which occurred after the second dose at 1200 mg Q3W.
Antitumor activity observed with an overall response rate of 16.7% (3/18), including 1 complete response and 2 partial responses (confirmed) in a difficult to treat population with no therapeutic options.
The disease control rate was 44.4% (8/18).
Typical IgG4 profile with linear pharmacokinetics (PK).
Planned Phase 2 studies utilizing recommended doses of either 500mg Q3W or 1000mg Q6W.
Title: Phase 2 Multicenter Trial of ICOS Agonist Vopratelimab and a CTLA-4 Inhibitor in PD-1/PD-L1 Inhibitor Experienced Adult Subjects with Non-Small Cell Lung Cancer or Urothelial Cancer (EMERGE)
Presentation Date and Time: Saturday, November 9, 2019, 7:00am – 8:30pm ET
Presenter: Russell K. Pachynski, M.D.
Abstract ID: P438

Jounce researchers highlight the scientific rationale for the ongoing Phase 2 EMERGE trial including:

Based on reverse translational findings from the ICONIC trial, strategies to optimize emergence and expansion of ICOS hi CD4 T cells have become a cornerstone of the vopratelimab development program.
The sequence of administration of ipilimumab and vopratelimab combination in EMERGE is designed to induce ICOS hi CD4 T cells with ipilimumab followed by their expansion and sustained activation by vopratelimab.
A pulsed dose and schedule for vopratelimab, designed to optimize agonist antibody activity, is explored. Specifically, the trial evaluates two different vopratelimab dose levels and a new dosing interval.
Both posters will be available on the "Our Pipeline" section of the Jounce Therapeutics website under "Publications" at www.jouncetx.com.

About Vopratelimab
Jounce’s lead product candidate, vopratelimab (formerly JTX-2011), is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab was previously assessed in the Phase 1/2 ICONIC trial and was found to be safe and well-tolerated, alone and in combination with each of the anti-PD-1 antibodies nivolumab and pembrolizumab, and ipilimumab, an antibody that binds to CTLA-4. In June 2018, Jounce reported Response Evaluation Criteria in Solid Tumors (RECIST) responses and other tumor reductions as determined by investigator assessment that were associated with an ICOS pharmacodynamic biomarker, ICOS hi CD4 T cells. In April 2019, Jounce reported data on patients in the ICONIC trial with the emergence of ICOS hi CD4 T cells who had improved progression free survival and overall survival compared to patients with ICOS lo CD4 T cells; this was based on an analysis of a subgroup of patients with multiple solid tumor types including PD-1 inhibitor naive and PD-1 inhibitor experienced patients. Vopratelimab is currently being assessed in the Phase 2 EMERGE clinical trial in combination with ipilimumab in patients with non-small cell lung cancer or urothelial cancer who have progressed on or after PD-1/PD-L1 inhibitor therapies.

About JTX-4014
JTX-4014 is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Jounce is developing JTX-4014 for potential use in combination with its pipeline of future product candidates. Jounce completed enrollment in the Phase 1 clinical trial of JTX-4014 and additional studies with JTX-4014 with our other product candidates are planned.

On November 5, 2019 Inovio Pharmaceuticals, Inc. (NASDAQ: INO) reported positive interim results from Inovio’s Phase 2 study (NCT03491683) of newly diagnosed glioblastoma multiforme (GBM) combining Inovio’s INO-5401, a T cell-activating immunotherapy encoding for three tumor-associated antigens (hTERT, WT1, and PSMA), and INO-9012, an immune activator encoding IL-12, in combination with Libtayo (cemiplimab), a PD-1 blocking antibody developed by Regeneron Pharmaceuticals (NASDAQ: REGN) in collaboration with Sanofi (Press release, Inovio, NOV 5, 2019, View Source [SID1234550328]). The data will be featured in a late-breaking poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2019 Annual Meeting in National Harbor, Maryland, November 6-10.

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

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

                  Schedule Your 30 min Free Demo!

Key interim data from the 52-patient clinical trial showed that 80% (16 of 20) of MGMT gene promoter methylated patients and 75% (24 of 32) of unmethylated patients were progression-free at six months (PFS6) measured from the time of their first dose, substantially exceeding historical standard-of-care data.

This immunotherapy combination with a PD-1 checkpoint inhibitor also exhibited supportive safety, tolerability, and immunogenicity data and suggested an acceptable safety profile consistent with that of Libtayo and Inovio’s platform technology. The majority of patients tested had a T cell immune response to one or more tumor-associated antigens encoded by INO-5401. Immune responses to all three tumor-associated antigens were demonstrated in this study. Inovio plans to report 12- and 18-month overall survival data next year.

Dr. David Reardon, M.D., Coordinating Principal Investigator of the study and the Clinical Director for Neuro-Oncology at the Dana-Farber Cancer Institute, said, "This innovative trial provides promising information that the combination of INO-5401 plus INO-9012, a T cell-promoting therapy, combined with Libtayo, a checkpoint inhibitor, may provide clinically meaningful benefit in this very difficult to treat disease."

Dr. J. Joseph Kim, Inovio’s President & CEO, said, "Our new data demonstrates the potential of our immunotherapies utilizing tumor-associated antigens in cancer treatments. Our goal in this GBM trial is to increase progression-free and overall survival of patients facing a disease where neither the standard of care nor clinical outcomes have significantly advanced in decades. Previously, other checkpoint inhibitor treatment alone in GBM trials did not show any meaningful clinical benefit over standard of care. However, the addition of INO-5401 and its ability to generate antigen-specific T cells demonstrated early efficacy signals in progression-free survival. We look forward to reporting additional data including overall survival at months 12 and 18 from the trial in the coming year."

Poster Details

Poster 858:

An Open-Label, Multi-center Trial of INO-5401 and INO-9012 Delivered by Electroporation (EP) in Combination with Cemiplimab in Subjects with Newly-Diagnosed Glioblastoma (GBM)

Category:

Late-Breaker

Date/Time:

Friday, Nov. 8th, 12:30 – 2 p.m. and Saturday, Nov. 9th 12:35 – 2:05 p.m.

Location:

Displayed in the Potomac Foyer (outside the Plenary session room, Potomac Ballroom)

Study Design

The trial was designed to evaluate safety, immunogenicity and preliminary efficacy of INO-5401 and INO-9012 in combination with Libtayo, with radiation and chemotherapy, in subjects with newly-diagnosed glioblastoma (GBM). This is a Phase 1/2, open-label, multi-center trial conducted in 52 evaluable patients with GBM. There were 2 cohorts in this trial. Cohort A were participants with a tumor with an unmethylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter. Cohort B included participants with a tumor with a MGMT methylated promoter or who have indeterminate MGMT status. Both cohorts received INO-5401 and INO-9012 and Libtayo at the same doses and on the same dosing schedule, and both cohorts received radiation and temozolomide (TMZ), if clinically indicated. Interim data presented here and at SITC (Free SITC Whitepaper) was obtained as of October 2019 and final study data is expected in Q4 2020. For more information of the clinical study, see www.clinicaltrials.gov, identifier NCT03491683.

About Glioblastoma Multiforme (GBM)

GBM is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the median progression-free survival is approximately 7 months. In the U.S., the estimated annual incidence of GBM is 11,362 cases or 3.21 cases per 100,000 persons and the median age at diagnosis is 65 years.

About INO-5401 and INO-9012

INO-5401 encodes for Inovio’s SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens were reported to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer. INO-9012 encodes for IL-12, which is a T cell immune activator.