On February 27, 2019 PRA Health Sciences, Inc. ("PRA" or the "Company") (NASDAQ: PRAH) reported financial results for the quarter and year ended December 31, 2018 (Press release, PRA Health Sciences, FEB 27, 2019, View Source;p=irol-newsArticle&ID=2389364 [SID1234533741])

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"We are delighted to have closed out 2018 with another quarter of strong financial results," said Colin Shannon, PRA’s Chief Executive Officer. "Our ability to execute across all of our businesses has allowed us to deliver solid revenue growth and strong bottom-line results. Our key financial metrics continue to improve, as highlighted by our 1.30 net book-to-bill ratio and our expanding margins. We remain focused on providing broad and flexible services to our clients and believe we are well positioned to deliver strong results in 2019."

Net new business for our Clinical Research segment for the three months ended December 31, 2018 was $667.3 million, representing a net book-to-bill ratio of 1.30 for the period. This net new business contributed to an ending backlog of $4.2 billion at December 31, 2018.

For the three months ended December 31, 2018, revenue was $729.6 million, which represents growth of 11.2%, or $73.8 million, compared to the fourth quarter of 2017 at actual foreign exchange rates. On a constant currency basis, revenue grew $79.0 million, an increase of 12.0% compared to the fourth quarter of 2017. By segment, the Clinical Research segment generated revenues of $655.6 million, while the Data Solutions segment generated revenues of $74.0 million.

On January 1, 2018, the Company adopted Accounting Standards Codification Topic 606, "Revenue from Contracts with Customers," or ASC 606, using the modified retrospective method for all contracts that were not completed as of January 1, 2018. Prior periods have not been restated under this guidance and remain as previously reported. The primary impact of applying this new guidance on our statement of operations is that (i) we now recognize reimbursements from our customers for payments to investigators as revenue, whereas these payments and costs were previously recorded on a net basis, and (ii) we include all reimbursed costs in the total project costs when measuring our progress under our research contracts instead of recording these amounts on a separate basis.

Excluding the impact of the adoption of ASC 606 and reimbursement revenue, revenue increased $20.2 million, which represents growth of 3.6% at actual foreign exchange rates and 4.2% on a constant currency basis.

Direct costs, exclusive of depreciation and amortization, were $365.7 million during the three months ended December 31, 2018 compared to $368.9 million for the three months ended December 31, 2017. The decrease in direct costs was primarily due to a favorable impact of $8.6 million from foreign currency exchange rate fluctuations, which was offset by an increase in salaries and related benefits of $3.6 million in our Clinical Research segment as we continue to ensure appropriate staffing levels and an increase of $1.6 million in our Data Solutions segment. Direct costs were 50.1% of revenue during the fourth quarter of 2018 compared to 56.2% of revenue during the fourth quarter of 2017. Excluding the impact of the adoption of ASC 606 and reimbursement revenue, direct costs were 62.1% of revenue during the fourth quarter of 2018 compared to 64.9% of revenue during the fourth quarter of 2017.

Selling, general and administrative expenses were $96.4 million during the three months ended December 31, 2018 compared to $92.2 million for the three months ended December 31, 2017. Excluding the impact of the adoption of ASC 606 and reimbursement revenue, selling, general and administrative costs were 16.4% of revenue during the fourth quarter of 2018 compared to 16.2% of revenue during the fourth quarter of 2017.

GAAP net income was $71.5 million for the three months ended December 31, 2018, or $1.07 per share on a diluted basis, compared to a GAAP net loss of $16.0 million for the three months ended December 31, 2017, or $0.25 per share on a diluted basis. Our reported net loss for the three months ended December 31, 2017 included the loss on modification of debt and the revaluation of acquisition-related earn-out liabilities.

EBITDA was $124.9 million for the three months ended December 31, 2018, representing an increase of 720.9% compared to the three months ended December 31, 2017. Our EBITDA for the three months ended December 31, 2017 included the loss on modification of debt and the revaluation of acquisition-related earn-out liabilities. Adjusted EBITDA was $136.2 million for the three months ended December 31, 2018, representing growth of 18.8% compared to the three months ended December 31, 2017.

Adjusted net income was $86.9 million for the three months ended December 31, 2018, representing 26.4% growth compared to the three months ended December 31, 2017. Adjusted net income per diluted share was $1.31 for the three months ended December 31, 2018, representing 26.0% growth compared to the three months ended December 31, 2017.

Full Year 2018 Financial Highlights

For the twelve months ended December 31, 2018, revenue was $2,871.9 million, which represents growth of 27.1%, or $612.5 million, compared to the twelve months ended December 31, 2017 at actual foreign exchange rates. On a constant currency basis, revenue grew $597.3 million, representing growth of 26.4% compared to the twelve months ended December 31, 2017. By segment, the Clinical Research segment generated revenues of $2,622.4 million, while the Data Solutions segment generated revenues of $249.5 million.

Excluding the impact of the adoption of ASC 606 and reimbursement revenue, revenue increased $348.5 million, which represents growth of 17.9% at actual foreign exchange rates and 17.4% on a constant currency basis. Organic revenue growth, excluding the adoption of ASC 606, reimbursement revenue and revenue attributable to our Data Solutions segment, was 10.2% at actual foreign exchange rates and 9.7% on a constant currency basis.

Reported GAAP income from operations was $281.3 million, reported GAAP net income attributable to PRA Health Sciences was $153.9 million and reported GAAP net income attributable to PRA Health Sciences per diluted share was $2.32 for the twelve months ended December 31, 2018.

Adjusted net income was $284.1 million for the twelve months ended December 31, 2018, an improvement of 29.8% compared to the twelve months ended December 31, 2017. Adjusted net income per diluted share was $4.28 for the twelve months ended December 31, 2018, up 28.5% compared to the twelve months ended December 31, 2017.

Full Year 2019 and Q1 2019 Guidance

For full year 2019, the Company expects to achieve total revenues between $3.09 billion and $3.20 billion, representing as reported and constant currency growth of 8% to 11%. On an ASC 605 basis, the Company expects to achieve revenues of between $2.475 billion and $2.57 billion, representing as reported and constant currency growth of 8% to 12%.

We expect GAAP net income per diluted share of between $3.65 and $3.80 per share and adjusted net income per diluted share of between $4.93 and $5.08 per share, representing growth of 15% to 19%. We anticipate an annual effective income tax rate estimate of 24%.

Our effective tax rate may differ from this estimate, due to, among other things, changes to estimates of the geographic allocation of our pre-tax income as well as changes in interpretations, analysis, and additional guidance that may be issued by regulatory agencies as it relates to the Tax Cuts and Jobs Act.

For Q1 2019, the Company expects to achieve total revenues between $720.0 million and $740.0 million, representing as reported growth of 3% to 5% and constant currency growth of 4% to 7%. On an ASC 605 basis, the Company expects to achieve revenues of between $575.0 million and $595.0 million, representing as reported growth of 3% to 6% and constant currency growth of 4% to 7%. The Company expects GAAP net income per diluted share of between $0.74 and $0.79 per share, adjusted net income per diluted share between $1.05 and $1.10 per share, and an annual effective income tax rate of 24%.

Our 2019 guidance assumes a EURO rate of 1.15 and a GBP rate of 1.35 with all other foreign currencies using a rate as of January 31, 2019.

A reconciliation of our non-GAAP measures, including revenue reported on an ASC 605 basis, EBITDA, adjusted EBITDA, adjusted net income, adjusted net income per share and our 2019 guidance, to the corresponding GAAP measures is included in this press release.

Conference Call Details

PRA will host a conference call at 9:00 a.m. ET on February 28, 2019, to discuss the contents of this release and other relevant topics. To participate, please dial (877) 930-8062 within the United States or (253) 336-7647 outside the United States approximately 10 minutes before the scheduled start of the call. The conference ID for the call is 8697447. The conference call will also be accessible, live via audio broadcast, on the Investor Relations section of the PRA website at investors.prahs.com. A replay of the conference call will be available online at investors.prahs.com. In addition, an audio replay of the call will be available for one week following the call and can be accessed by dialing (855) 859-2056 within the United States or (404) 537-3406 outside the United States. The replay ID is 8697447.

Additional Information

A financial supplement with fourth quarter 2018 results, which should be read in conjunction with this press release, may be found in the Investor Relations section of our website at investors.prahs.com in a document titled "Q4 2018 Earnings Presentation."

On February 27, 2019 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company developing novel cancer immunotherapies based on tumor-infiltrating lymphocyte (TIL) technology, reported its fourth quarter and year-end 2018 financial results and provided a corporate update (Press release, Iovance Biotherapeutics, FEB 27, 2019, View Source [SID1234533740]).

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"Over the past year, we took great strides forward in our goal of advancing TIL therapy towards approval in multiple indications and bringing this one-time treatment to patients who have progressed through existing treatment options," commented Maria Fardis, Ph.D., MBA, president and chief executive officer of Iovance Biotherapeutics. "We reported clinical results for our lead program in metastatic melanoma, received acknowledgement from the FDA on a defined path to approval with a single-arm study and have firmly established our optimized, scalable, 22-day manufacturing process. We are well financed to complete the registration-enabling study, Cohort 4, and file the Biologics License Application (BLA) in 2020 for lifileucel. The regenerative medicine advanced therapy (RMAT) designation we received this past year for lifileucel allows for close coordination with the FDA as we move forward. Now that we have demonstrated compelling data in post PD-1 melanoma patients and have received regulatory clarity, we continue our development work in additional indications, such as cervical, while preparing to build internal manufacturing capabilities. Our goals for 2019 will further propel Iovance towards registration and commercialization of TIL therapy."

2018 Highlights

Clinical

·New data from Cohort 2 of lifileucel in the treatment of metastatic melanoma study (C-144-01) was presented in poster and oral presentations at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in November 2018. The presentation described results from 47 consecutively dosed, post PD-1 patients with an objective response rate (ORR) of 38%.1 The most common treatment emergent adverse events observed in this cohort include thrombocytopenia, chills, neutropenia, febrile neutropenia and anaemia.
·In the Phase 2 study of LN-145 for cervical carcinoma (C-145-04) preliminary data was reported in October 2018 for 15 patients yielding an ORR of 27%. Patients in the study had a median of five prior therapies. The safety findings from this study remained consistent with previous reports.

Regulatory

·In May 2018, the company was granted orphan drug designation from the U.S. Food and Drug Administration (FDA) for autologous tumor infiltrating lymphocytes for the treatment of cervical cancer with a tumor size of greater than 2 cm in diameter.
·In September 2018, the company received the Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for lifileucel for the treatment of patients with metastatic melanoma.
·In September 2018, the company held an end of Phase 2 meeting with the FDA during which the agency acknowledged that a single-arm cohort as part of the C-144-01 study can be supportive of initial registration of lifileucel.

Research

·Under a collaboration with Ohio State University, Iovance has developed a product candidate called peripheral blood lymphocytes (PBL). The company anticipates filing an IND for PBL in hematological indications in 2019.

Corporate

·The company completed two underwritten public offerings in 2018 raising approximately $400 million.

2019 Updates

Clinical

·The protocol for the metastatic melanoma study (C-144-01) was amended based on FDA feedback. The trial sites are in process of re-activation for Cohort 4, which is expected to enroll 75 patients. Patient enrollment has commenced.
·The last patient was enrolled in Cohort 2 of the metastatic melanoma study in the fourth quarter of 2018. The company anticipates providing an update on the full cohort of patients at a medical meeting in 2019.
·The protocol for the cervical carcinoma study has been amended to limit the number of prior therapies to no more than three and to exclude patients who have been treated with prior immunotherapy. The company anticipates providing an update on this study at an upcoming medical meeting in 2019.
·The company has dosed over 100 patients with the Gen 2 manufacturing product across multiple studies.

Regulatory

·In February 2019, the company was granted Fast Track designation from the FDA for treatment of patients with recurrent, metastatic, or persistent cervical cancer patients who have progressed while on or after chemotherapy.

Research

·An abstract titled "Persistence of cryopreserved tumor-infiltrating lymphocyte product lifileucel (LN-144) in C-144-01 study of advanced metastatic melanoma" was accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting March 29-April 3, 2019.

Fourth Quarter 2018 Financial Results

Net loss for the fourth quarter 2018 was $32.6 million, or $0.27 per share, compared to net loss of $25.9 million or $0.36 per share for the fourth quarter 2017.

Research and Development expenses were $27.4 million for the fourth quarter 2018, an increase of $6.7 million compared to $20.7 million for the quarter ended December 31, 2017. The increase in Research and Development expenses is attributable to; an increase in Research and Development staff and the related compensation expense, an increase in clinical trial and manufacturing costs due to the initiation of clinical trials in 2018 for new indications and increased number of patients enrolled across all the studies.

General and administrative expenses were $7.5 million for the fourth quarter 2018, an increase of $2.1 million compared to $5.4 million for the fourth quarter ended 2017. The increase in General and Administrative expenses was primarily attributable to an increase in General and Administrative headcount and related compensation expenses and an increase in external professional service fees.

Full Year 2018 Financial Results

Net loss for the year ended December 31, 2018 was $123.6 million, or $1.27 per share, compared to $92.1 million or $1.41 per share for the year ended December 31, 2017.

Research and Development expenses were $99.8 million for the year ended December 31, 2018, an increase of $28.2 million compared to $71.6 million for 2017. The increase was primarily attributable to an increase in payroll and related expenses, including stock-based compensation expenses, due to a higher number of full-time employees and dedicated consultants as we expanded our internal research efforts and clinical development programs. Further, clinical trial costs increased due to; higher patient enrollment and an increase in the number of clinical sites for lifileucel and LN-145.

General and Administrative expenses were $28.4 million for the year ended December 31, 2018, an increase of $7.1 million compared to $21.3 million for 2017. The increase was primarily attributable to an increase in payroll and related expenses, including stock-based compensation expenses, driven by a higher number of full-time employees and higher stock prices during 2018, and an increase in external professional service fees including preparation and filing of patents.

Cash, Cash Equivalents and Short-term Investments

At December 31, 2018, the company held $468.5 million in cash, cash equivalents and short-term investments, compared to $145.4 million at December 31, 2017. Net cash used in operating activities was $101.2 million during the year ended December 31, 2018.

Iovance anticipates cash, cash equivalents and investments to be between $310 million and $320 million at December 31, 2019.

Webcast and Conference Call

Iovance will host a conference call and live audio webcast to discuss financial results and provide a corporate update today at 4:30 p.m. ET.

To participate in the conference call, please dial 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and reference the access code 7055329. The live webcast can be accessed under "News & Events" in the Investors section of the Company’s website at www.iovance.com, or you may use the link: View Source

A replay of the call will be available from February 27, 2019 at 7:00 p.m. ET to March 6, 2019 at 6:30 p.m. ET. To access the replay, please dial 1-855-859-2056 (domestic) or 1-404-537-3406 (international) and reference the access code 7055329. The archived webcast will be available for thirty days in the Investors section at www.iovance.com.

1 The ORR included one complete response and 17 partial responses, one of which was unconfirmed and pending patient’s subsequent clinical assessment.

On February 27, 2019 vTv Therapeutics Inc. (Nasdaq:VTVT) reported financial results for the fourth quarter and year that ended December 31, 2018, and provided an update on recent achievements and upcoming events (Press release, vTv Therapeutics, FEB 27, 2019, View Source;p=RssLanding&cat=news&id=2389244 [SID1234533739]).

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"We are excited about the therapeutic potential of azeliragon in patients with mild-Alzheimer’s Disease (AD) and type 2 diabetes and our progress to date with our Simplici-T1 trial in type 1 diabetics," said Steve Holcombe, chief executive officer, vTv Therapeutics. "Our licensing partners also continue to advance our GLP-1R agonist, PPAR-delta, and PDE4 programs and we hope to see progress in each of these programs over the next year."

Recent Achievements and Outlook

Initiated start-up activities for an adaptive Phase 2/3 clinical trial for azeliragon as a potential treatment of mild AD in patients with type 2 diabetes. Post-hoc subgroup analyses of our phase 3 STEADFAST Study identified that a population of mild-AD patients with type 2 diabetes experienced positive benefit. Based on these results, we have initiated start-up activities for an adaptive Phase 2/3 trial to evaluate azeliragon as a potential treatment of mild-AD in patients with type 2 diabetes. We are currently finalizing a protocol for the study, negotiating with clinical research organizations to support study conduct activities for the trial and beginning the site selection process. We expect to initiate patient enrollment in this study in mid-2019. We plan to continue to develop azeliragon through internal efforts, based upon receipt of additional funding, or through future partnerships with other life science entities.
Simplic-T1 Study enrolling patients with type 1 diabetes. We have completed enrollment of the part 1 learning phase of the adaptive Phase 1/2 Simplici-T1 Study, a 12-week study to evaluate TTP399 as an add-on to insulin therapy for type 1 diabetics, and expect to report results for this portion of the study in June 2019. We have begun the start-up activities for the part 2 confirmatory phase and expect to report results for this portion of the study in the latter part of the first quarter of 2020. TTP399 has previously demonstrated statistically significant reductions in HbA1c levels in the AGATA Study, a phase 2 study in type 2 diabetes.
Financing Strategy. We are evaluating several financing strategies to fund the proposed clinical trial of azeliragon for the treatment of mild-AD in patients with type 2 diabetes, including direct equity investment and future public offerings of our common stock. The timing and availability of such financing are not yet known.
Fourth Quarter 2018 Financial Results

Cash Position: Cash and cash equivalents as of December 31, 2018, were $1.7 million compared to $3.8 million as of September 30, 2018.
R&D Expenses: Research and development expenses were $2.8 million in the fourth quarter of 2018 which were consistent with the $2.7 million of such expenses incurred in the third quarter of 2018.
G&A Expenses: General and administrative expenses were $2.1 million and $2.2 million in the fourth and third quarters of 2018, respectively.
Net Loss Before Non-Controlling Interest: Net loss before non-controlling interest was $2.3 million for the fourth quarter of 2018 compared to net loss before non-controlling interest of $2.0 million for the third quarter of 2018.
Net Loss Per Share: GAAP net loss per share was $0.10 and $0.06 for the three months ended December 31, 2018 and September 30, 2018, respectively, based on weighted-average shares of 17.6 million and 12.3 million for the three month periods ended December 31, 2018 and September 30, 2018, respectively. Non-GAAP net loss per fully exchanged share was $0.08 and $0.06 for the three months ended December 31, 2018 and September 30, 2018, respectively, based on non-GAAP fully exchanged weighted-average shares of 40.7 million and 35.4 million for the three months ended December 31, 2018 and September 30, 2018, respectively.
Full Year 2018 Financial Results

R&D Expenses: Research and development expenses were $23.0 million and $39.6 million for the years ended December 31, 2018 and 2017, respectively. The decrease in research and development expenses was primarily driven by the termination of the STEADFAST and open label extension studies and related activities in the second quarter of 2018.
G&A Expenses: General and administrative expenses were $9.2 million and $11.3 million for the years ended December 31, 2018 and 2017, respectively. The decrease in general and administrative expenses was primarily due to decreases in expenses for share-based awards, incentive-based compensation and professional services.
Net Loss Before Non-Controlling Interest: Net loss before non-controlling interest was $23.8 million and $54.6 million for the years ended December 31, 2018 and 2017, respectively.
Net Loss Per Share: GAAP net loss per share was $0.69 and $1.67 for the years ended December 31, 2018 and 2017, respectively, based on weighted-average shares of 12.4 million and 9.7 million for the years ended December 31, 2018 and 2017, respectively. Non-GAAP net loss per fully exchanged share was $0.69 and $1.67 for the year ended December 31, 2018 and 2017, respectively, based on non-GAAP fully exchanged weighted-average shares of 35.5 million and 32.8 million for the years ended December 31, 2018 and 2017, respectively.

On February 27, 2019 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that it will host a conference call and webcast to report its fourth quarter and fiscal year 2018 financial results on Wednesday, March 6, 2018, at 8:30 a.m. ET (Press release, GlycoMimetics, FEB 27, 2019, View Source [SID1234533738]).

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The dial-in number for the conference call is (844) 413-7154 for domestic participants and (216) 562-0466 for international participants, with participant code 5072004. A webcast replay will be available via the "Investors" tab on the GlycoMimetics website for 30 days following the call. A dial-in phone replay will be available for 24 hours after the close of the call by dialing (855) 859-2056 for domestic participants and (404) 537-3406 for international participants, participant code 5072004.

On February 27, 2019 ImmunoGen, Inc., (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that 11 posters highlighting continued innovation in the field of ADCs will be presented at the upcoming American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting to be held March 29 – April 3, 2019 in Atlanta, Georgia (Press release, ImmunoGen, FEB 27, 2019, View Source [SID1234533737]).

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"ImmunoGen remains at the forefront of ADC innovation and the data to be presented at AACR (Free AACR Whitepaper) further demonstrate the value of our productive research platform," said Richard Gregory, Ph.D., ImmunoGen’s chief scientific officer.

The schedule of ImmunoGen’s presentations at AACR (Free AACR Whitepaper) is as follows:

IGN Payload Innovation

Title: Antibody-drug conjugates (ADCs) of a new class of N-10 amino linked DNA alkylating indolino-benzodiazepines (IGNs) – abstract #224
Date: March 31, 2019
Time: 1:00-5:00 PM ET

In an ongoing effort to further explore the structure-activity relationship of DNA alkylating effector molecules for ADCs, a new class of IGNs has been developed that possesses a self-immolative peptide linker attached at the N-10 amine of the imine-reduced IGN monomer subunit. ADCs with this class of payload displayed potent, antigen-specific in vitro activity across a panel of folate receptor α (FRα)-expressing cell lines.
Title: Antibody-drug conjugates (ADCs) with indolinobenzodiazepine dimer (IGN) payloads: DNA-binding mechanism of IGN catabolites in target cancer cells – abstract #1886
Date: March 31, 2019
Time: 1:00-5:00 PM ET

Investigation of the mechanism of binding of IGN catabolites with DNA in target cancer cells and with model duplex DNA or hairpin oligonucleotides. Both mono-and-di-imine IGN molecules remained bound to genomic DNA even at two days, suggesting a potent interaction with cellular DNA.
Advancement in Platform Linkers and Payloads

Title: Optimizing lysosomal activation of antibody-drug conjugates (ADCs) by incorporation of novel cleavable dipeptide linkers – abstract #0231
Date: March 31, 2019
Time: 1:00-5:00 PM ET

Based on screens of a panel of dipeptide linkers for efficient lysosomal proteolysis, several novel, previously unreported peptide linker designs were identified and incorporated into ADCs bearing a DNA-alkylating IGN payload. Several dipeptide linker designs were superior in rates of lysosomal processing compared to a reference standard L-Ala-L-Ala dipeptide linker.
Title: LC-MS based catabolite identification study of an ADC with DM21-C, a novel maytansinoid linker-payload – abstract #538
Date: March 31, 2019
Time: 1:00-5:00 PM ET

ImmunoGen’s newest ADC design uses the novel maytansinoid linker-payload, DM21-C that bears a peptidase/protease-cleavable linker. The goal of this study was to identify the catabolites generated upon incubation in antigen-positive cancer cells (both cell pellet and media), in mouse plasma, as well as in in vitro catabolic systems. DM51 (the thiol- resulting from self-immolation of the cleaved linker-payload) was identified as a major catabolite of the DM21-C ADC.
Title: Preclinical evaluation of DM21, a next‐generation maytansinoid payload with a stable peptide linker – abstract #3898
Date: April 2, 2019
Time: 1:00-5:00 PM ET

To evaluate the toxicity of DM21 as an ADC, it was conjugated to the non‐targeting, chimeric anti‐soybean trypsin inhibitor antibody (chKTI), and administered to cynomolgus monkeys in two groups with separate dose levels. chKTI‐DM21 was well-tolerated at both doses.
Novel Approaches to ADC Development

Title: Generation of site-specific DARPin drug conjugates using EGFR as a model system – abstract #215
Date: March 31, 2019
Time: 1:00-5:00 PM ET

DARPin molecules are small engineered proteins, derived from natural ankyrin repeat proteins that are selected to bind to specific targets with high affinity. DARPin drug conjugates (DDCs) were developed using a model EGFR multi-specific DARPin molecule, consisting of four DARPin domains linked together. Biophysical characterization showed the DDCs to be well behaved in stability and solubility assays.
Title: Development of a Probody-Drug Conjugate (PDC) targeting EpCAM for the treatment of solid tumors- abstract #1439
Date: March 31, 2019
Time: 1:00-5:00 PM ET

EpCAM is an attractive target for ADC development due to its overexpression on a variety of tumors of epithelial origin; however, EpCAM is also expressed on a variety of normal epithelia, thus limiting its utility as an ADC target due to potential toxicity. We aim to overcome this limitation by developing an EpCAM-targeting Probody drug conjugate (PDC). EpCAM-targeting PDCs were better tolerated than the corresponding EpCAM-targeting ADC even at higher dose levels and displayed longer half-lives and greater exposure.
Title: IMGC936, a first-in-class ADAM9-targeting antibody-drug conjugate, demonstrates promising anti-tumor activity – abstract #5136
Date: April 1, 2019
Time: 8:00 AM-12:00 PM ET

Under a co-development agreement with MacroGenics, it has been shown that ADAM9 is overexpressed in multiple solid tumor indications and that anti-ADAM9 antibodies are efficiently internalized and degraded by tumor cell lines, making ADAM9 an attractive target for ADC development. IMGC936 is the first ADAM9-targeting ADC to enter preclinical development. In vitro studies have demonstrated targeted cytotoxicity of IMGC936 across a panel of ADAM9-positve tumor cell lines with activity at least 2 logs greater than a non-targeting conjugate. Consistent with the activity observed in vitro, an anti-ADAM9-DM21 conjugate displayed compelling anti-tumor activity in multiple xenograft models representing non-small cell lung, gastric and colorectal cancers.
Title: Preclinical evaluation of a new, non-agonist ADC targeting MET-amplified tumors with a peptide-linked maytansinoid – abstract #4817
Date: April 3, 2019
Time: 8:00 AM-12:00 PM ET

cMet is an attractive target for ADCs, which may address the unmet treatment need for patients with tumors harboring MET amplification. To assess potential toxicity due to normal tissue expression, binding of our antibody to normal hepatocytes from humans and cynos was measured. Very low expression and binding versus tumor cell lines were found and demonstrated that the cytotoxic activity of disulfide-cleavable maytansinoid ADCs prepared from the hinge-variant cMet antibody was equivalent to the parental form in in vivo models. These data merit further exploration of this ADC as a novel treatment option for patients with MET-amplified tumors.
Optimizing ADC Dosing

Title: The potential benefit of lower drug-antibody ratio (DAR) on antibody-maytansinoid conjugate in vivo efficacy – abstract #219
Date: March 31, 2019
Time: 1:00-5:00 PM

Describes development of a cross-reactive model system that utilizes a chimeric anti-murine FRα antibody that binds with similar affinity to mouse and human FRα. Using this cross-reactive system, where the target is also expressed in normal tissues, 2.0 DAR conjugates were more efficacious than 3.5 DAR conjugates when dosed at matched payload concentrations in multiple xenograft models, suggesting that lower DAR can be an effective strategy to compensate for target-mediated drug disposition (TMDD).
Title: Utilizing a mouse cross-reactive model system to better understand antibody-drug conjugate pharmacokinetics, biodistribution and efficacy – abstract #229
Date: March 31, 2019
Time: 1:00-5:00 PM ET

Generation of a cross-reactive model system that utilized a chimeric anti-murine FRα antibody that binds both mouse and human FRα and can be conjugated to either maytansinoid or IGN payloads. This model system was predicted to have substantial TMDD due to normal tissue expression of FRα. The results showed that TMDD significantly affected the pharmacokinetics, biodistribution, and activity of the conjugate relative to a non-cross-reactive ADC, with lower ADC doses being more severely impacted than higher doses.
Additional information and full abstracts can be found at www.aacr.org.