On November 9, 2018 Synthorx, Inc., a biotechnology company using a first-of-its-kind Expanded Genetic Alphabet platform technology to discover and develop optimized biologics for cancer and autoimmune disorders, reported company researchers will present results of preclinical studies demonstrating the safety and anti-tumor effects of its lead product candidate THOR-707, a "not-alpha" Synthorin of interleukin-2 (IL-2), for the treatment of solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting (Press release, Synthorx, NOV 9, 2018, View Source [SID1234531204]). Marcos Milla, Ph.D., chief scientific officer of Synthorx, will present the poster on Friday, November 9, from 12:45 – 2:15 p.m. and 6:30 – 8:00 p.m. ET at the Walter E. Washington Convention Center in Washington, D.C.

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The study, titled "THOR-707: An engineered IL-2 for the treatment of solid tumors with superior preclinical efficacy and safety evidence," investigates the application of Synthorx’s Expanded Genetic Alphabet platform technology to engineer THOR-707, a variant of recombinant human IL-2 that is pegylated at one specific site and designed to kill tumor cells without inducing vascular leak syndrome (VLS), a toxicity associated with aldesleukin, an approved recombinant IL-2. Aldesleukin was approved by the U.S. Food and Drug Administration over 25 years ago for the treatment of patients with metastatic renal cell carcinoma and metastatic melanoma. However, widespread use of aldesleukin has been limited by toxicities, which include life-threatening and sometimes fatal VLS, as well as by its short half-life, requiring courses of dosing of three times per day over eight days.

In Synthorx’s preclinical studies, THOR-707 induces molecular markers of T cell activation and the proliferation of peripheral NK and CD8+ effector T cells in vivo. However, dosing of THOR-707 has minimal effect on molecular and clinical markers of VLS, even at high exposures. Analysis of the effect of THOR-707 in syngeneic mouse tumor models showed that THOR-707 induced infiltration of CD8+ T effector cells into tumors and elicited anti-tumor effects alone and in combination with a PD-1 immune checkpoint inhibitor.

On November 12, 2018 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH), reported exploratory subgroup analyses and preliminary translational data from the Phase II trial evaluating the combination of monalizumab and cetuximab (anti-EGFR) in previously treated patients with recurrent and/or metastatic squamous cell carcinoma of the head & neck (R/M SCCHN) (Press release, Innate Pharma, NOV 9, 2018, View Source [SID1234531226]). Monalizumab is a first-in-class checkpoint inhibitor targeting NKG2A inhibitory receptors expressed on tumor-infiltrating cytotoxic CD8 T lymphocytes and NK cells.

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"The subgroup analysis revealed very interesting durable responses in both IO-naïve and IO-pretreated patients," commented Pierre Dodion, Chief Medical Officer of Innate Pharma. "Patients who have failed on IO-therapy currently have no other treatment option. The fact that they appear to benefit with prolonged survival is rather remarkable and prompted us to advance our clinical program. Discussions are taking place in parallel with regards to the next steps in IO naïve patients".

"The high disease control rate that we observed in this study along with the favorable trends in progression-free and overall survival, including a preliminary estimate of median overall survival of 10.3 months, are very encouraging," commented Professor Roger B. Cohen, Principal Investigator of the study. "We also saw evidence of clinical activity in both IO-naive and IO-pretreated patients. If confirmed, these data would provide support for a highly novel immunotherapeutic combination with a unique mechanism of action for the treatment of patients with head & neck cancer."

Data from the cohort of 40 patients were reported at 2018 ESMO (Free ESMO Whitepaper) congress in October. Exploratory subgroup analysis revealed encouraging responses, durability of response, PFS and OS in IO-naïve and IO-pretreated patients.

Cut-off August 31, 2018

All patients

(n=40)

IO-naïve

(n=23)

IO-pretreated

(n=17)

ORR [95% CI]

27.5% [16-43]

35% [19-55]

18% [6-41]

Median PFS [95% CI]

5.0 m [3.7-6.9]

4.0 m[3.7-10.6]

5.0 m [3.5-NR]

Median OS [95% CI]

10.3 m [7.3-NR]

10.3 m [7.2-NR]

12.8 m [6.0-NR]

DCR 24 weeks

35% [22-51]

39% [22-59]

29% [13-53]

Median time to response [range]

1.6 m [1.5-3.9]

1.7 m [1.5-3.9]

1.6 m [1.6-3.1]

Median duration of response [95% CI]

5.6 m [3.8-NR]

5.3 m [3.8-NR]

5.6 m [3.7-NR]

Eric Vivier, Chief Scientific Officer of Innate Pharma, said: "We are combining the use of state-of-the-art technologies including high-dimensional flow cytometry, single cell RNA seq and computational pathology, to monitor the immune response in patients. Data support the mode of action of monalizumab as unleashing a multilayered immune response involving both NK and T cells. As such, monalizumab appears as a first-in-class second generation immune checkpoint inhibitor with a large spectrum of immune targets. He added: "While preliminary, translational results suggest that the combination of monalizumab and cetuximab is associated with a reshaping of "cold tumors" into "hot tumors" prone to sustain tumor immunity".

Preliminary biomarker analysis show indeed that while the combination did not impair the distribution or absolute counts of peripheral NKG2A+ NK and CD8+ T cells, an infiltration of NK cells and CD8+T cells is detected very early upon treatment (day 15) at the tumor bed. Further, tumor-infiltrating NK and CD8+ T cells may be predictive of RECIST response, tumor reduction and PFS.

Importantly, the activity of the monalizumab and cetuximab combination appears to occur across HPV status, tumor burden and PD-L1 expression.

On November 8, 2018 Cambrex Corporation (NYSE: CBM), a leading manufacturer of small molecule innovator and generic Active Pharmaceutical Ingredients ("APIs"), and finished dosage forms, reported its results for the third quarter ended September 30, 2018 (Press release, Cambrex, NOV 8, 2018, View Source;p=irol-newsArticle&ID=2376146 [SID1234530924]).

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Third Quarter 2018 Highlights

Completed the acquisition of Halo Pharma ("Halo"), a leading finished dosage form Contract Development and Manufacturing Organization ("CDMO") specializing in product development and commercial manufacturing, for $425 million in total cash consideration.

Net revenue decreased 7% under current U.S. GAAP, ASC 606 – Revenue from Contracts with Customers ("ASC 606"). Under ASC 605, the previous revenue recognition standard, Net revenue decreased 9% compared to the same quarter last year.

Under ASC 606, Diluted EPS from continuing operations was $0.79 per share compared to $0.52 per share in the same quarter last year. 2018 performance reflects a lower tax rate resulting from tax reform in the United States and New Jersey. Under ASC 605, Diluted EPS from continuing operations would have been $0.94 per share.

Under ASC 606, EBITDA decreased to $15.8 million from $33.7 million in the same quarter last year. Adjusted EBITDA, which excludes the impact of adopting ASC 606, Halo’s results and acquisition and integration costs, was $28.1 million (see table at the end of this press release).

Net debt was $227.9 million at the end of the quarter, an increase of $399.2 million during the quarter primarily driven by the acquisition of Halo Pharma and partially offset by cash flows from operations during the quarter.

The Company now expects full year 2018 Adjusted Net revenue, which excludes the impact of foreign currency and the adoption of ASC 606, to be between -1% and -3% compared to 2017 and Adjusted EBITDA to be between $153 and $159 million, excluding the impact of the Halo acquisition (see Financial Expectations – Continuing Operations section below for related explanations and additional financial guidance).
"We’re very pleased to have closed the Halo acquisition this quarter, which diversifies our business into the large, growing market for outsourced finished dosage form contract development and manufacturing. Halo’s capabilities complement Cambrex’s existing global API manufacturing expertise and Halo expands our customer base and broadens our small molecule funnel. Integration is well underway and we are confident that this business will allow us to better meet the needs of our global network of customers and create future growth synergies," commented Steven M. Klosk, President and Chief Executive Officer of Cambrex.

"Market conditions in the Innovator sector remain strong and the addition of a new late stage project during the third quarter brings our total to 18 such products. A key component of our long term growth strategy is to steadily increase the number of late stage products in our portfolio. We believe that Cambrex is increasingly well positioned to execute against this strategy."

Basis of Reporting
The Company has provided a reconciliation of GAAP to adjusted (i.e. Non-GAAP) amounts at the end of this press release. Cambrex management believes that the adjustments provide useful information to investors due to the magnitude and nature of certain amounts recorded under GAAP.

Third Quarter 2018 Operating Results – Consolidated, Continuing Operations
Net revenue under ASC 606 was $104.6 million. Under ASC 605, the previous revenue recognition standard, Net revenue decreased to $102.7 million, or 9%, from $112.6 million in the same quarter last year. Net revenue during the quarter includes the acquisition of Halo which contributed revenue of $5.2 million under ASC 606 and $6.3 million under ASC 605. Results under ASC 606 and ASC 605 include a 1% unfavorable impact of foreign exchange compared to the third quarter of 2017.

Gross margins under ASC 606 were 31%. Under ASC 605, gross margins were 38% compared to 42% in the same quarter last year.

Selling, general and administrative expenses were $14.5 million, compared to $17.2 million in the same quarter last year. The decrease was mainly due to lower personnel related costs, an accounts receivable write-off in the same quarter last year and the impact of foreign currency.

Research and development expenses were flat year over year at $4.2 million.

Acquisition and integration expenses of $7.4 million represents costs associated with the acquisition of Halo.

Operating profit under ASC 606 was $6.6 million. Under ASC 605, operating profit was $13.2 million compared to $25.5 million in the same quarter last year. The decrease was primarily the result of higher operating expenses related to the purchase of Halo and lower gross profit. Adjusted EBITDA was $28.1 million compared to $33.7 million in the same quarter last year (see table at the end of this press release).

Income tax expense was a benefit of $15.4 million compared to an expense of $7.5 million and an effective tax rate of 30% in the same quarter last year. The income tax benefit during the quarter reflects the immediate recognition of certain effects of share-based compensation, acquisition and integration expenses, unrealized gain on investment in equity securities, a $2.1 million benefit for the finalization of the toll charge on undistributed foreign earnings under U.S. tax reform, and a $12.2 million benefit for the release of a state valuation allowance and the revaluation of state deferred tax balances due to New Jersey tax reform enacted during the third quarter of 2018. Excluding these items, the effective tax rate would have been approximately 20% during the quarter.

Income from continuing operations under ASC 606 was $26.8 million or $0.79 per share.

Adjusted income from continuing operations, calculated under ASC 605 and including other adjustments described in the table at the end of this press release, was $16.7 million or $0.49 per share, compared to $18.5 million or $0.55 per share in the same quarter last year.

Capital expenditures were $10.8 million and depreciation and amortization was $9.2 million compared to $15.4 million and $8.2 million, respectively, in the same quarter last year.

Net debt was $227.9 million at the end of the third quarter, an increase of $399.2 million during the quarter. The increase was driven by the acquisition of Halo and partially offset by cash flows from operations.

Third Quarter 2018 Operating Results – Finished Dosage Form ("FDF") segment
The acquisition of Halo resulted in the creation of the FDF segment for Cambrex. Included in Cambrex’s consolidated results for the third quarter of 2018 are the results of Halo for the period from acquisition date, September 12, 2018, through September 30, 2018 and are as follows.

Net revenue in the third quarter of 2018 under ASC 606 was $5.2 million. Net revenue under ASC 605 was $6.3 million.

Gross margins under ASC 606 in the third quarter of 2018 were 32%. Gross margins under ASC 605 were 28%.

Selling, general and administrative expenses were $1.1 million in the third quarter of 2018.

Operating profit under ASC 606 was $0.5 million. Under ASC 605, operating profit was $0.6 million. Both exclude $0.4 million in integration costs and includes increased depreciation and amortization expense resulting from the application of purchase accounting.

Financial Expectations – Continuing Operations
The following table shows the Company’s current expectations for its full year 2018 financial performance versus its expectations from the previous quarter. The expectations in the table below reflect expected results from the business excluding the recent acquisition of Halo and are consistent with the basis on which prior guidance was provided.

On November 8, 2018 Caladrius Biosciences, Inc. (Nasdaq: CLBS) ("Caladrius" or the "Company"), a late-stage therapeutics development biopharmaceutical company with multiple technology platforms targeting select cardiovascular indications and autoimmune disease, reported its financial results for the three ended September 30, 2018, and provides a business update (Press release, Caladrius Biosciences, NOV 8, 2018, View Source [SID1234530965]).

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Highlights of the 2018 third quarter and early fourth quarter include:

Continued enrollment in a Phase 2 (SAKIGAKE designated and eligible for early conditional approval) clinical trial in Japan of CLBS12 for the treatment of no-option critical limb ischemia ("CLI"), including completion of enrollment of the five patient Buerger’s disease cohort;

Continued enrollment in a Phase 2 clinical trial using the CD34 cell therapy CLBS14-CMD for the treatment of coronary microvascular dysfunction ("CMD");

Continued follow-up analysis of The Sanford Project: T-Rex Study Phase 2 clinical trial of CLBS03 in type 1 diabetes after completing enrollment and reporting six-month results on 50% of trial subjects in the first quarter of 2018 that concluded the treatment is well-tolerated and non-futile for therapeutic effect; and

Conducted a Type B meeting with the US Food and Drug Administration ("FDA") under the provisions of the RMAT designation for CLBS14-RfA for the treatment of refractory angina to define remaining steps to registration.

"We are pleased with the advancement of our clinical programs during the third quarter. We maintain our previous guidance regarding development milestones and continue to demonstrate efficient management of cash spend," stated Dr. David J. Mazzo, President and CEO. "The fully-enrolled T-Rex Study of CLBS03 in type 1 diabetes remains on track for top-line data in early 2019. Our programs studying our CD34 cell therapy platform for CMD here in the United States and CLI in Japan continue to enroll with a target for top-line data in the second half of 2019 and early 2020, respectively.

"We are also pleased to announce that we recently completed our Type B meeting with the FDA pertaining to CLBS14-RfA for the treatment of refractory angina. This meeting was conducted to obtain FDA guidance and to define the remaining requirements for registration of this product under the terms of its RMAT designation. We believe that the meeting was both collaborative and positive and our assessment of the conversation is that FDA is demonstrating maximum flexibility afforded under the RMAT designation as we work together to establish the development steps necessary to bring this product to registration. We will be working with FDA to finalize the next development steps and to formalize the minutes of the meeting. We look forward to providing further information once these actions are completed."

Third Quarter Financial Highlights

Research and development expenses for the third quarter of 2018 were $1.7 million, a 47% decrease compared with $3.2 million for the third quarter of 2017. The current quarter expenses were principally comprised of costs in our ischemic repair programs for CLBS12 and CLBS14-CMD, as well as initial planning for our CLBS14-RfA

program. Conversely, the prior year quarter expenses were primarily focused on our T-Rex study for CLBS03, which completed enrollment in December 2017 and is now in the follow-up phase of the study.

General and administrative expenses for the third quarter of 2018 were $2.1 million, a 30% decrease compared with $2.9 million for the third quarter of 2017, due to lower general and administrative headcount and corporate-related activities compared with the prior year period.

The net loss from continuing operations for the third quarter of 2018 was $3.5 million, or $0.36 per share, compared with $3.5 million, or $0.38 per share, for the third quarter of 2017.

Nine Month Financial Highlights

Research and development expenses for the nine months ended September 30, 2018 were $6.1 million, a 46% decrease compared with $11.2 million for the nine months of 2017. The current year expenses were principally comprised of costs in our ischemic repair programs for CLBS12 and CLBS14-CMD as well as initial planning for our CLBS14-RfA program. Conversely, the prior year expenses were primarily focused on our T-Rex study for CLBS03, which completed enrollment in December 2017 and is now in the follow-up phase of the study.

General and administrative expenses for the nine months ended September 30, 2018 were $7.1 million, a 22% decrease compared with $9.1 million for the nine months of 2017. The decrease was due to lower general and administrative headcount and corporate-related activities compared with the prior year period, along with the sale of our counter-flow centrifugation system to Hitachi in the second quarter of 2018, which resulted in a one-time $1.4 million gain included in general and administrative expenses.

The net loss from continuing operations for the nine months ended September 30, 2018 was $12.6 million, or $1.31 per share, compared with $25.8 million, or $1.37 per share, for the nine months of 2017.

Balance Sheet Highlights

As of September 30, 2018, Caladrius had cash, cash equivalents and marketable securities of $46.1 million, compared with $60.1 million as of December 31, 2017. Based on existing programs and projections, the Company continues to remain confident that its cash balances and additional grant funding, along with continued disciplined expense management, will allow it to fund its current business plan beyond 2019.

Conference Call

Caladrius management will host a conference call for the investment community today beginning at 4:30 p.m. Eastern time to review financial results, provide a Company update and answer questions.

Stockholders and other interested parties may participate in the conference call by dialing (866) 595-8403 (domestic), or (706) 758-9979 (international), and providing conference ID: 9490459. The call will also be broadcast live on the Internet via the Company’s website at www.caladrius.com/investors/news-events.

For those unable to participate on the live conference call, a replay will be available through November 15, 2018, and can be accessed by dialing (855) 859-2056 or (404) 537-3406. All listeners should provide the following replay access code: 9490459.

The webcast replay will be archived on the Company’s website for 90 days at www.caladrius.com.

On November 8, 2018 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 third quarter 2018 business highlights and financial results (Press release, Kezar Life Sciences, NOV 8, 2018, View Source [SID1234531020]).

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"During the third quarter of 2018 we continued to execute on our strategy of developing our first-in-class selective immunoproteasome inhibitor for patients with severe autoimmune diseases. Enrollment continues in KZR-616-002, our Phase 1b/2 trial in lupus (SLE) and lupus nephritis (LN), with top-line results from the initial two cohorts of the Phase 1b expected in the first half of 2019," said John Fowler, CEO of Kezar. "In the same timeframe we plan to begin enrolling the Phase 2 portion of the trial, focused exclusively on LN, a serious disease with high medical and economic burden and no approved drugs. Plans to initiate trials in up to four additional autoimmune indications with high unmet need are also on track for 2019."

Business Highlights

Enrollment of patients with SLE with or without nephritis to the open-label dose escalation Phase 1b portion of the clinical trial KZR-616-002 (NCT03393013), continued in the third quarter. This trial will include a randomized, placebo-controlled Phase 2 portion in patients with active, proliferative LN.

Ongoing drug discovery efforts in the protein secretion program (Sec61 translocon modulation) advanced in the third quarter. Continued progress with the medicinal chemistry campaign and preclinical studies could lead to nomination of a first clinical candidate for oncology in 2019.

Financial Results

Cash Position. Cash, cash equivalents and marketable securities totaled $112.8 million as of September 30, 2018, compared to $51.0 million as of December 31, 2017. The increase in cash, cash equivalents and marketable securities was primarily attributable to IPO proceeds, net of cash used by the Company in operations to advance its clinical stage programs as well as preclinical research and development.

R&D Expenses. Research and development expenses for the third quarter of 2018 increased by $3.1 million to $4.7 million from $1.6 million in the third quarter of 2017. This increase was primarily related to advancing both the KZR-616 clinical program and the protein secretion preclinical program.

G&A Expenses. General and administrative expenses for the third quarter of 2018 increased by $1.0 million to $1.6 million from $0.6 million in the third quarter of 2017. This increase was primarily related to increases in personnel, professional services and insurance incurred because of becoming a public company.

Net Loss. Net loss for the third quarter of 2018 was $5.7 million, or $0.30 per basic and diluted common share, compared to a net loss of $2.1 million, or $3.31 per basic and diluted common share, for the third quarter of 2017.

Shares Outstanding. Total shares outstanding were 19.1 million as of September 30, 2018. Additionally, there were 2.2 million options granted to purchase common stock at a $3.70 weighted average exercise price as of September 30, 2018.