On February 25, 2021 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported operational highlights and financial results for the fourth quarter and year ended December 31, 2020 (Press release, Intellia Therapeutics, FEB 25, 2021, View Source [SID1234575597]).

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!

"Intellia’s achievements in 2020 reflect important progress on both our full-spectrum strategy and our mission to deliver curative genome editing treatments for people with severe diseases. Dosing our first patient with NTLA-2001, the first-ever systemically delivered CRISPR-based therapy, was a major milestone for our team, as we completed our transition to a clinical-stage company in the fourth quarter," said Intellia President and Chief Executive Officer, John Leonard, M.D. "Looking ahead, we are focused on our three core priorities for 2021: clinical validation of our approach with NTLA-2001, advancement and expansion of our in vivo and ex vivo pipeline, and continued platform innovation. We have made steady progress in our global Phase 1 study of NTLA-2001 and look forward to sharing our first clinical data this year. Additionally, we are on track to submit first-in-human regulatory applications to begin clinical studies of NTLA-5001 for AML and NTLA-2002 for HAE, and we plan to nominate at least one new development candidate from our research portfolio."

Fourth Quarter 2020 and Recent Operational Highlights

NTLA-2001 for ATTR: NTLA-2001 is the first systemically delivered CRISPR-based therapy dosed in a patient and could potentially be the first curative treatment for ATTR. By applying the Company’s in vivo lipid nanoparticle (LNP) delivery technology, NTLA-2001 offers the possibility of halting and reversing the disease with potent, lifelong transthyretin (TTR) protein reduction after a single course of treatment. NTLA-2001 is part of a co-development/co-promotion agreement between Intellia, the lead party, and Regeneron Pharmaceuticals, Inc. (Regeneron).

The Company anticipates reporting interim clinical data from the Phase 1 study this year. These results are expected to characterize the emerging safety and activity profile of NTLA-2001 at the initial dose levels.
In November, Intellia dosed the first patient in its global Phase 1 study evaluating NTLA-2001 in adults with hereditary ATTR with polyneuropathy (hATTR-PN). The Company continues to enroll patients in the study and is submitting additional regulatory applications in other countries as part of its ongoing, global development strategy.
Intellia intends to evaluate NTLA-2001 in a broader ATTR population of both polyneuropathy and cardiomyopathy patients following its Phase 1 safety assessment and dose optimization.
NTLA-5001 for AML: NTLA-5001 is a potential best-in-class engineered T cell therapy designed to treat all genetic subtypes of AML. This investigational candidate is an autologous T cell receptor (TCR)-T cell therapy targeting the Wilms’ Tumor 1 (WT1) antigen utilizing Intellia’s proprietary cell engineering process.

Intellia plans to submit an Investigational New Drug (IND) application or equivalent regulatory application for NTLA-5001 in mid-2021. This first-in-human trial is expected to evaluate the safety and activity of NTLA-5001 in patients with persistent or recurrent AML who have previously received first-line therapies.
NTLA-5001 shows high anti-tumor activity in proof-of-concept mouse models of acute leukemias. The preclinical data presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December highlighted faster expansion and superior function of T cells manufactured by Intellia’s proprietary approach, compared to standard T cell engineering approaches currently in use.
The Company is also evaluating the potential use of NTLA-5001 to treat WT1-positive solid tumors in preclinical studies.
NTLA-2002 for HAE: NTLA-2002 aims to prevent attacks for people living with HAE after a single course of treatment. Intellia is applying its modular LNP delivery system to develop NTLA-2002 to knock out the KLKB1 gene in the liver to permanently reduce plasma kallikrein activity. This approach is expected to provide continuous suppression of kallikrein activity and eliminate the significant treatment burden associated with currently available therapies for HAE patients.

Intellia commenced clinical manufacturing activities to support the Company’s plans to submit an IND or equivalent regulatory application in the second half of 2021.
The Company is applying insights gained from NTLA-2001 to expedite clinical development of NTLA-2002. The first-in-human trial is expected to evaluate safety, tolerability and activity in patients with HAE.
The Company plans to present additional preclinical results in support of NTLA-2002 at the upcoming American Academy of Allergy, Asthma & Immunology (AAAAI) 2021 Annual Meeting, taking place virtually from February 26 – March 1, 2021.
Modular Platform and Pipeline Expansion: Intellia is advancing its modular platform technologies to broaden the in vivo and ex vivo applications of genome editing. This includes developing capabilities for innovative CRISPR/Cas9-mediated in vivo editing in multiple tissue types, targeted transgene insertion and an allogeneic approach for the development of "off-the-shelf" T cell therapies. These efforts will support new therapeutic candidates for genetic diseases requiring removal and/or restoration of a protein, and next-generation engineered cell therapies for cancers and auto-immune diseases.

Intellia plans to nominate at least one additional development candidate in 2021 and expects to present preclinical data at upcoming scientific conferences highlighting research advancements and platform innovations.
Intellia demonstrated the modularity of its targeted insertion approach for a second target, in non-human primates, showing insertion of the SERPINA1 gene produced normal levels of human alpha-1 antitrypsin (AAT) after a single administration. In December, these results were presented at the Alpha-1 Foundation’s 20th Gordon L. Snider Critical Issues Workshop: The Promise of Gene-Based Interventions of Alpha-1 Antitrypsin Deficiency. Intellia is advancing multiple genome editing strategies that may treat both lung and liver manifestations of AAT deficiency (AATD), which occur due to mutations in the SERPINA1 gene.
Intellia is advancing preclinical validation of in vivo hematopoietic stem cell (HSC) genome editing using the Company’s proprietary non-viral delivery systems and CRISPR/Cas9 technology to potentially cure sickle cell disease. This research is supported by a grant from the Bill & Melinda Gates Foundation.
Financing: In December, Intellia closed an underwritten public offering of 5,513,699 shares of common stock, including the exercise in full of the underwriters’ option to purchase additional shares, at the public offering price of $36.50 per share. Intellia received aggregate gross proceeds of approximately $201 million, before underwriting discounts and commissions and offering expenses.
Upcoming Events

The Company will participate in the following events during the first quarter of 2021:

AAAAI Annual Meeting, February 26–March 1, Virtual
Keystone Symposium: Precision Engineering of the Genome, Epigenome and Transcriptome, March 8-10, Virtual
Barclays Capital Global Healthcare Conference, March 8, Virtual
Oppenheimer’s 31st Annual Healthcare Conference, March 16, Virtual
Cold Spring Harbor Laboratories meeting on Nucleic Acid Therapies, March 24 – 26, Virtual
Upcoming Milestones

The Company has set forth the following for pipeline progression:

ATTR: Report initial clinical data from Phase 1 study of NTLA-2001 in 2021
AML: Submit an IND or IND-equivalent for NTLA-5001 in mid-2021
HAE: Submit an IND or IND-equivalent for NTLA-2002 in 2H 2021
Nominate at least one new development candidate in 2021
Fourth Quarter and Full-Year 2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $597.4 million as of December 31, 2020, compared to $284.5 million as of December 31, 2019. The increase was driven by net proceeds of $296.6 million from our follow-on public offerings, $100.0 million upfront payment from the Regeneron collaboration expansion, which included a $30.0 million equity investment, $49.5 million of net equity proceeds raised from the Company’s "At the Market" (ATM) agreement, $18.2 million from the Regeneron and Novartis Institutes for BioMedical Research, Inc. (Novartis) collaborations and $13.2 million in proceeds from employee-based stock plans. These increases were offset in part by cash used to fund operations of approximately $164.6 million.
Collaboration Revenue: Collaboration revenue decreased by $4.3 million to $6.6 million during the fourth quarter of 2020, compared to $10.9 million during the fourth quarter of 2019. The decrease was primarily driven by a decrease in Novartis revenue as the research portion of the collaboration ended in December 2019.
R&D Expenses: Research and development expenses increased by $6.5 million to $38.2 million during the fourth quarter of 2020, compared to $31.7 million during the fourth quarter of 2019. This increase was primarily driven by the advancement of our lead programs, research personnel growth to support these programs and expansion of the development organization.
G&A Expenses: General and administrative expenses increased by $1.8 million to $10.8 million during the fourth quarter of 2020, compared to $9.0 million during the fourth quarter of 2019. This increase was primarily related to employee related expenses, including stock-based compensation of $1.3 million.
Net Loss: The Company’s net loss was $42.2 million for the fourth quarter of 2020, compared to $28.3 million during the fourth quarter of 2019.
Financial Guidance

Intellia expects that its cash, cash equivalents and marketable securities as of December 31, 2020 will enable the Company to fund its robust R&D plans, anticipated operating expenses and capital expenditure requirements at least through the next 24 months. This expectation excludes any strategic use of capital not currently in the Company’s base-case planning assumptions.

Conference Call to Discuss Fourth Quarter and Full-Year 2020 Earnings

The Company will discuss these results on a conference call today, February 25, 2021, at 8 a.m. ET.

To join the call:

U.S. callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call.
All participants should ask to be connected to the Intellia Therapeutics conference call.
A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia’s website at www.intelliatx.com, beginning on February 25, 2021 at 12 p.m. ET.

On February 25, 2021 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and reported financial results for the year ended December 31, 2020 (Press release, MacroGenics, FEB 25, 2021, View Source [SID1234575635]).

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!

"Following the approval in late 2020 of our first drug with the U.S. Food and Drug Administration (FDA), 2021 has the potential to be another transformative year for MacroGenics. We expect to launch MARGENZA in the coming weeks and will continue to advance our deep pipeline of promising product candidates in multiple clinical trials," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We are particularly excited about our ongoing, potentially registration-enabling studies, including flotetuzumab in acute myeloid leukemia (AML) and margetuximab in gastric cancer, as well as two Prescription Drug User Fee Act (PDUFA) target action dates in July related to retifanlimab and teplizumab. And finally, we look forward to providing clinical updates on multiple, ongoing dose expansion studies this year."

Key Updates on Proprietary Programs

Recent progress and anticipated events in 2021 related to MacroGenics’ approved and investigational product candidates in clinical development, as well as an advanced preclinical program, are highlighted below.

Margetuximab is an Fc-engineered, monoclonal antibody (mAb) that targets the HER2 oncoprotein, which is expressed by certain breast, gastroesophageal and other solid tumor cells.

MARGENZA (margetuximab-cmkb) approval and commercial launch. In December 2020, the FDA approved MARGENZA in combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. The launch, which is being coordinated with MacroGenics’ commercial partner, EVERSANA, is expected in March.
Phase 2/3 MAHOGANY study in advanced gastric (GC) and gastroesophageal junction (GEJ) cancer. The MAHOGANY clinical program contains two modules designed to evaluate margetuximab as an investigational agent in combination with a checkpoint inhibitor, with or without chemotherapy, as a potential first-line treatment for patients with advanced or metastatic HER2-positive GC/GEJ. Initial safety and efficacy data from among the first 40 patients enrolled in Module A, which is evaluating margetuximab in combination with retifanlimab (an anti-PD-1 therapy), are expected in the first half of 2021. Enrollment in Module B, which is evaluating margetuximab plus MacroGenics’ checkpoint inhibitor molecules in combination with chemotherapy compared to standard of care therapy of trastuzumab with chemotherapy in patients with HER2-positive tumors irrespective of PD-L1 expression, is currently ongoing in coordination with the Company’s regional partner in Greater China, Zai Lab.
Flotetuzumab is a bispecific CD123 × CD3 DART molecule being evaluated in patients with primary induction failure (PIF) and early relapsed (less than six months, or ER6) AML. Six clinical and preclinical abstracts related to AML and flotetuzumab were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition in December 2020. MacroGenics is conducting a single-arm, registration-enabling clinical study to evaluate flotetuzumab in up to 200 patients with PIF/ER6 AML, with complete remission (CR) and CR with partial hematological recovery (CRh) as the composite primary endpoint. The Company anticipates providing further updates on the clinical development of flotetuzumab in the second half of 2021, and completing full enrollment of this study in 2022.
MGC018 is an antibody-drug conjugate that targets B7-H3. MacroGenics continues to enroll patients with metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) in the dose expansion portion of the Phase 1 clinical study. The Company expects to provide an update on this study in mid-2021.
Enoblituzumab is an Fc‐engineered, anti‐B7‐H3 mAb. In the coming weeks, MacroGenics expects to initiate a Phase 2 study of enoblituzumab in a chemo-free regimen in combination with retifanlimab in front-line patients with squamous cell carcinoma of the head and neck (SCCHN) who are PD-L1 positive and with tebotelimab in SCCHN patients who are PD-L1 negative.
Tebotelimab is a bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab is being evaluated in a Phase 1 dose expansion study as monotherapy in several tumor types. An oral presentation of tebotelimab Phase 1 data in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) was made at ASH (Free ASH Whitepaper) in December 2020. In addition, data from the combination study of tebotelimab and margetuximab in patients with advanced HER2+ neoplasms were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November 2020. MacroGenics’ regional partner in Greater China, Zai Lab, is also evaluating tebotelimab in Phase 1 combination studies with niraparib and brivanib for the study of advanced gastric cancer and hepatocellular carcinoma, respectively, as well as a monotherapy study in patients with melanoma. MacroGenics expects to provide clinical updates on tebotelimab in 2021, including future development plans.
MGD019 is a bispecific, tetravalent DART molecule targeting PD-1 and CTLA-4. The Company is enrolling Phase 1 dose expansion cohorts, initially in patients with microsatellite stable colorectal cancer (MSS CRC) and checkpoint-naïve NSCLC at the recommended Phase 2 dose. The Company expects to provide a clinical update on this study in mid-2021.
IMGC936 is an antibody-drug conjugate that targets ADAM9, a cell surface protein over-expressed in several solid tumor types. IMGC936 is being advanced under a co-development agreement with ImmunoGen, Inc. Under the 50/50 collaboration, ImmunoGen is leading clinical development and the Phase 1 dose escalation study is currently enrolling patients with select advanced solid tumors.
MGD024 is a next-generation, bispecific CD123 × CD3 DART molecule in preclinical development. The molecule incorporates a CD3 component designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, along with an Fc domain to permit intermittent dosing through a longer half-life. The Company anticipates submitting an Investigational New Drug (IND) application to the FDA by the end of 2021.
Key Partnered Programs Update

Recent progress and disclosed priorities for MacroGenics’ partnerered investigational molecules are highlighted below.

Retifanlimab is an anti-PD-1 mAb that has been exclusively licensed to Incyte Corporation. To date, MacroGenics has earned $65 million in milestones related to retifanlimab, triggered by advancement of the molecule through various clinical and regulatory activities. In January 2021, Incyte announced that the FDA had accepted for Priority Review its Biologics License Application (BLA) for retifanlimab as a potential treatment for adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal. The PDUFA target action date for retifanlimab is July 25, 2021. MacroGenics is eligible to receive up to a total of $685 million in potential remaining development, regulatory and commercial milestones. If retifanlimab is approved and commercialized, MacroGenics would be eligible to receive royalties, tiered from 15 to 24 percent, on future worldwide net sales of the drug.
Teplizumab is a mAb being developed by Provention Bio, Inc. for the treatment of type 1 diabetes. In January 2021, Provention announced the FDA filing of a BLA and Priority Review for this molecule, with a PDUFA target action date of July 2, 2021. In 2018, MacroGenics sold its interest in teplizumab to Provention and is eligible to receive up to $170 million upon the achievement of certain regulatory approval milestones, including $60 million upon approval of a BLA in the U.S., additional milestone payments totaling $225 million upon the achievement of certain sales milestones and single-digit royalties on net sales of the molecule.
Corporate Updates

Janssen Collaboration. In December 2020, MacroGenics announced a research collaboration and global license agreement to develop a preclinical bispecific molecule with Janssen Biotech, Inc. The research collaboration will incorporate MacroGenics’ proprietary DART platform to enable simultaneous targeting of two undisclosed targets in a therapeutic area outside oncology. Under the terms of the agreement, Janssen paid MacroGenics an upfront payment of $20 million and will be responsible for funding all expenses. MacroGenics will also be eligible to receive up to $312 million in potential milestone payments and tiered royalties on worldwide product sales.
Ms. Federica O’Brien Added to Board. MacroGenics recently announced the appointment of Federica "Freddi" O’Brien, a veteran executive with 25 years of financial and operational leadership in biopharmaceutical, medical device, and technology companies, to its Board of Directors.
2020 Financial Results

Cash Position: Cash, cash equivalents and marketable securities as of December 31, 2020 were $272.5 million, compared to $215.8 million as of December 31, 2019.
Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $104.9 million for the year ended December 31, 2020, compared to $64.2 million for the year ended December 31, 2019. This increase was primarily due to the recognition of milestones, partially offset by timing of revenue recognition under the Company’s collaborative agreements.
R&D Expenses: Research and development expenses were $193.2 million for the year ended December 31, 2020, compared to $195.3 million for the year ended December 31, 2019.
G&A Expenses: General and administrative expenses were $42.7 million for the year ended December 31, 2020, compared to $46.1 million for the year ended December 31, 2019. This decrease was primarily due to a decrease in external costs, including consulting.
Net Loss: Net loss was $129.7 million for the year ended December 31, 2020, compared to net loss of $151.8 million for the year ended December 31, 2019.
Shares Outstanding: Shares outstanding as of December 31, 2020 were 56,244,771.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities as of December 31, 2020, as well as anticipated and potential collaboration payments, should enable it to fund its operations into 2023, assuming the Company’s programs and collaborations advance as currently contemplated.
Conference Call Information

MacroGenics will host a conference call today at 4:30 pm (ET) to discuss financial results for the year ended December 31, 2020 and provide a corporate update. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 6094343.

The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

IMPORTANT SAFETY INFORMATION – MARGENZA
BOXED WARNING: LEFT VENTRICULAR DYSFUNCTION AND EMBRYO-FETAL TOXICITY

Left Ventricular Dysfunction: MARGENZA may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate cardiac function prior to and during treatment. Discontinue MARGENZA treatment for a confirmed clinically significant decrease in left ventricular function.
Embryo-Fetal Toxicity: Exposure to MARGENZA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.
WARNINGS & PRECAUTIONS:

Left Ventricular Dysfunction

Left ventricular cardiac dysfunction can occur with MARGENZA.
MARGENZA has not been studied in patients with a pretreatment LVEF value of <50%, a prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV.
Withhold MARGENZA for ≥16% absolute decrease in LVEF from pre-treatment values or LVEF below institutional limits of normal (or 50% if no limits available) and ≥10% absolute decrease in LVEF from pretreatment values.
Permanently discontinue MARGENZA if LVEF decline persists greater than 8 weeks, or dosing is interrupted more than 3 times due to LVEF decline.
Evaluate cardiac function within 4 weeks prior to and every 3 months during and upon completion of treatment. Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan.
Monitor cardiac function every 4 weeks if MARGENZA is withheld for significant left ventricular cardiac dysfunction.
Embryo-Fetal Toxicity

Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman. Post-marketing studies of other HER-2 directed antibodies during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Verify pregnancy status of women of reproductive potential prior to initiation of MARGENZA.
Advise pregnant women and women of reproductive potential that exposure to MARGENZA during pregnancy or within 4 months prior to conception can result in fetal harm.
Advise women of reproductive potential to use effective contraception during treatment and for 4 months following the last dose of MARGENZA.
Infusion-Related Reactions (IRRs)

MARGENZA can cause IRRs. Symptoms may include fever, chills, arthralgia, cough, dizziness, fatigue, nausea, vomiting, headache, diaphoresis, tachycardia, hypotension, pruritus, rash, urticaria, and dyspnea.
Monitor patients during and after MARGENZA infusion. Have medications and emergency equipment to treat IRRs available for immediate use.
In patients experiencing mild or moderate IRRs, decrease rate of infusion and consider premedications, including antihistamines, corticosteroids, and antipyretics. Monitor patients until symptoms completely resolve.
Interrupt MARGENZA infusion in patients experiencing dyspnea or clinically significant hypotension and intervene with supportive medical therapy as needed. Permanently discontinue MARGENZA in all patients with severe or life-threatening IRRs.
MOST COMMON ADVERSE REACTIONS:

The most common adverse drug reactions (≥10%) with MARGENZA in combination with chemotherapy are fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, infusion-related reactions, palmar-plantar erythrodysesthesia, and extremity pain.

On February 25, 2021 AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company developing first-in-class antibody product candidates focused on emerging immune control mechanisms applicable to inflammation and immuno-oncology indications, reported operating results for the fourth quarter and year ended December 31, 2020 and provided pipeline updates (Press release, AnaptysBio, FEB 25, 2021, View Source [SID1234575663]).

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 made progress in advancing AnaptysBio’s pipeline during 2020 and look forward to multiple clinical readouts from our wholly-owned programs in 2021. Imsidolimab will continue to be our key focus going forward as we anticipate GPP Phase 3 initiation and Phase 2 topline readouts from five other immune-dermatology indications through 2021 and 2022. We also anticipate commercial launch of dostarlimab this year and meaningful milestone and royalty revenue to AnaptysBio under our GSK partnership," said Hamza Suria, president and chief executive officer of AnaptysBio. "Our strategy is to continue advancing first-in-class immunology-focused therapeutic antibodies through key clinical data catalysts using a capital-efficient business model."

Imsidolimab (Anti-IL-36 Receptor) Program

In July, we announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for imsidolimab, our proprietary anti-interleukin-36 receptor (IL-36R) antibody, for the treatment of patients with GPP.
In October, we announced positive topline data from an interim analysis of our imsidolimab GALLOP Phase 2 trial in GPP. Six of 8 patients achieved the primary endpoint of disease improvement upon Day 29, while erythema with skin pustules, which clinically defines GPP, decreased by 94% on Day 29 relative to baseline. We plan to report 16-week data from the GALLOP trial at a medical conference in 2021.
We anticipate initiation of a Phase 3 trial for imsidolimab in GPP during mid-2021 following completion of protocol alignment, and review of 16-week data from the Phase 2 GALLOP trial, with the FDA.
We are also conducting a randomized, placebo-controlled, multi-dose Phase 2 trial in 59 patients with palmoplantar pustulosis, or PPP, also known as the POPLAR trial, with topline data anticipated in Q1 2021.
We have expanded our imsidolimab program into third and fourth new clinical indications, EGFRi-mediated skin toxicities and ichthyosis, with interim top-line data from Phase 2 trials anticipated at the end of 2021 and in 2022, respectively, and we are also expanding the imsidolimab program into fifth and sixth new clinical indications, hidradenitis suppurativa and acne, with initiation of Phase 2 trials in these indications anticipated in Q2 2021.
We initiated a worldwide registry of GPP and PPP patients, named RADIANCE, in Q1 2021, to improve understanding of the patient journey and support enrollment of future trials.
ANB030 (Anti-PD-1 Agonist) Program

We anticipate topline data from our ongoing Phase 1 healthy volunteer clinical trial of ANB030, our wholly-owned PD-1 agonist antibody, designed to assess the safety, pharmacokinetics and pharmacodynamics of ANB030 in single and multiple ascending dose cohorts in mid-2021.
Preclinical translational data using ANB030 was presented in March 2020 at the Festival of Biologics Meeting.
We anticipate initiating Phase 2 trials of ANB030 in alopecia areata and vitiligo in Q4 2021.
ANB032 (Anti-BTLA Modulator) Program

We filed a Clinical Trial Notification ("CTN") in Australia for ANB032, our wholly-owned BTLA modulator antibody, during the first quarter of 2021 and anticipate initiating a healthy volunteer Phase 1 trial in the first half of 2021 upon clearance of the CTN.
We presented preclinical data regarding ANB032 at the 2020 Federation of Clinical Immunology Societies (FOCIS) Virtual Annual Meeting in October 2020.
Etokimab (ANB020 Anti-IL-33) Program

We discontinued further development of etokimab, our anti-IL-33 antibody previously referred to as ANB020, following review of topline week 16 data from the approximately 100-patient ECLIPSE trial in chronic rhinosinusitis with nasal polyps (CRSwNP), where patients dosed with etokimab every four (q4w) or eight weeks (q8w) failed to achieve statistically significant over placebo on either co-primary endpoint.
Dostarlimab (Anti-PD-1 Antagonist) Program Partnered with GSK

In October 2020, we amended our immuno-oncology collaboration with GSK resulting in increased financial consideration to AnaptysBio. Royalties due to AnaptysBio for dostarlimab were increased to 8-25% of global net sales, where AnaptysBio will receive 8% of annual global net sales below $1 billion, and 12-25% of net sales above $1 billion. The $1.1 billion in cash milestone payments due under the collaboration agreement remain unchanged, and AnaptysBio anticipates receiving $75 million in such cash milestones over the next 18 months as dostarlimab obtains FDA and EMA regulatory approval for the first two indications. An additional $165 million in sales milestones is anticipated by AnaptysBio upon achievement of certain dostarlimab annual sales revenues. GSK also agreed, starting January 1, 2021, to pay AnaptysBio a 1% royalty on all of GSK’s global net sales of Zejula. In addition, GSK paid AnaptysBio a one-time cash payment of $60 million in Q4 2020. In exchange, AnaptysBio provided GSK with freedom to conduct development and commercialization of Zejula in combination with third-party molecules and settled the dispute between AnaptysBio and GSK.
US BLA and European Union EMA approvals for dostarlimab are anticipated for endometrial cancer in H1 2021, which will result in $20 million and $10 million milestone payments, respectively. The FDA recently accepted a subsequent US BLA for dostarlimab in pan-deficient mismatch repair tumors and we anticipate receiving a $10 million payment from GSK in Q1 2021 as a result of this milestone.
Board of Directors

In January 2021, the Company appointed Dr. Magda Marquet to its board of directors. She is the co-founder of AltheaDx, a commercial stage, precision medicine company, and co-founded Althea Technologies and as its co-CEO led the company to become a highly profitable, commercial company. Prior to starting Althea Technologies, Dr. Marquet held several positions in pharmaceutical development in companies such as Vical and Amylin Pharmaceuticals. She currently serves on the Board of Directors of Arcturus Therapeutics, Micronoma, Matrisys Biosciences and ProciseDx.
Fourth Quarter Financial Results

Cash, cash equivalents and investments totaled $411.2 million as of December 31, 2020 compared to $428.5 million as of December 31, 2019, for a net decrease of $17.3 million. The decrease relates primarily to cash used for operating activities partially offset by an increase in collaboration revenue of $67.0 million.
Collaboration revenue was $60.0 million and $75.0 million for the three and twelve months ended December 31, 2020, which related to milestone payments for successful BLA and MAA filings for dostarlimab and the $60.0 million amendment related payment from GSK, compared to $3.0 million and $8.0 million for the three and twelve months ended December 31, 2019.
Research and development expenses were $21.6 million and $80.0 million for the three and twelve months ended December 31, 2020, compared to $21.4 million and $99.3 million for the three and twelve months ended December 31, 2019. The annual decrease was due primarily to reduced outside services for manufacturing and clinical activities based on the timing of projects.
General and administrative expenses were $5.1 million and $18.9 million for the three and twelve months ended December 31, 2020, compared to $3.8 million and $16.1 million for the three and twelve months ended December 31, 2019. The increase was due primarily to increased legal and insurance expenses.
Net income was $33.6 million for the three months ended December 31, 2020, or a net income per share of $1.23 and a net loss of $19.9 million for the twelve months ended December 31, 2020, or a net loss per share of $0.73, compared to a net loss of $20.3 million and $97.3 million for the three and twelve months ended December 31, 2019, or a net loss per share of $0.75 and $3.60.
Financial Guidance

AnaptysBio expects its net cash burn in 2021 will be close to $100 million. We anticipate that our cash, cash equivalents and anticipated revenues will fund our current operating plan at least into 2024.

On February 25, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, and UCLA Technology Development Group (UCLA TDG) reported an agreement to develop novel therapeutic antibodies, pairing novel targets proposed by scientists at UCLA and utilizing Xencor’s modular suite of XmAb technology platforms (Press release, Xencor, FEB 25, 2021, View Source [SID1234575679]). Xencor and UCLA have established a streamlined framework to select promising biology, perform collaborative research and license intellectual property.

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!

Xencor’s XmAb platforms are precisely engineered antibody Fc domains, which enable the creation of stable new protein structures, such as bispecific antibodies and engineered cytokines, or amplification of natural immune functions, such as extending circulating half-life or enhancing immune cell cytotoxicity. Xencor and its pharmaceutical partners are now advancing 20 clinical-stage XmAb-engineered drug candidates for the treatment of patients with life-threatening and debilitating diseases. Two of these antibodies have been approved by the U.S. FDA, one for the treatment of patients with rare blood disorders and the other for an aggressive form of non-Hodgkin lymphoma.

"The creation of exciting new therapeutic modalities requires advancing innovative biological concepts together with state-of-the-art molecular platforms to build best-in-class biologics," said John Desjarlais, Ph.D., senior vice president and chief scientific officer at Xencor. "The inherent modularity and stability provided by our XmAb platforms, and our ability to precisely tune a molecule’s target-binding capability, opens the door to evaluate the clinical potential of biology that was previously considered intractable. We look forward to collaborating with UCLA’s investigators to translate their biological insights into potential medicines."

The UCLA Technology Development Group, the campus’ gateway to innovation, research and entrepreneurship, will work with faculty to propose potential antibody drug candidates. For selected candidates, the collaborators will use a framework with predefined terms to enter sponsored research agreements and potential license agreements.

"Many revolutionary medical breakthroughs discovered by UCLA’s world-class investigators have vastly improved the care of patients, including engineered T cells, therapeutic antibodies and small molecules that are now approved to treat many types of cancer," said Amir Naiberg, Associate Vice Chancellor, Chief Executive Officer and President of the UCLA Technology Development Group.

"With this collaboration, we aim to accelerate the development of potential new biologic medicines, leveraging Xencor’s protein engineering technologies and expertise and the ongoing scientific discoveries and insights into disease biology made at UCLA, with the ultimate goal to improve patient outcomes and quality of life," added Mark A. Wisniewski, Senior Director of Biopharmaceuticals at UCLA TDG.

On February 25, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage biotechnology company developing drugs to treat cancers with the greatest medical need for new treatment options, including KRAS-mutated colorectal cancer, pancreatic cancer, castrate-resistant prostate cancer and leukemias, reported recent company highlights and financial results for the fourth quarter and full year ended December 31, 2020 (Press release, Cardiff Oncology, FEB 25, 2021, View Source [SID1234575717]).

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!

"Over the last several months we achieved key clinical milestones, which provided the momentum for our successful raise of over $100 million. Together, these events have enabled us to accelerate the execution of our clinical programs and expand our pipeline to other relevant cancer indications," said Dr. Mark Erlander, chief executive officer of Cardiff Oncology. "Data from our lead KRAS-mutated metastatic colorectal cancer (mCRC) program show promising and durable efficacy, highlighting the potential of onvansertib in combination with standard-of-care FOLFIRI (irinotecan and 5-FU)/bevacizumab to address the need for a new second-line treatment option. Importantly, we completed enrollment in the Phase 1b portion of this trial in December of 2020 and initiated patient accrual in the Phase 2 segment in January of this year. Based on the mCRC trial results, we are leveraging the known synergy of onvansertib with irinotecan and 5-FU by evaluating this combination (nanoliposoamal irinotecan and 5-FU) in pancreatic ductal adenocarcinoma (PDAC). Approximately 95% of PDAC patients have a KRAS mutation and current second-line treatment for this indication conveys only a 7.7% response rate and 6-month median overall survival benefit. We plan to initiate a Phase 2 trial in this indication in the first half of the year following the receipt of our "study may proceed" notification from the FDA last month. Our goal is to further demonstrate the broad applicability of onvansertib across KRAS-mutated cancers and to address an indication with a significant unmet need for new treatment options."

Dr. Erlander continued, "Onvansertib’s broad applicability extends beyond targeting KRAS-mutated cancers, as shown by the exciting progress of our metastatic castrate-resistant prostate cancer (mCRPC) trial. The addition of onvansertib to daily abiraterone treatment in patients showing initial resistance to abiraterone has resulted in durable disease control. Notably, the most recent data presented at ASCO (Free ASCO Whitepaper)-GU showed a significant increase in disease control rate in patients receiving onvansertib for more days within a treatment cycle. Looking ahead, the progress we’ve made across our clinical programs leaves us poised to achieve a steady cadence of catalysts throughout 2021 and beyond as we continue to advance onvansertib’s development."

Program highlights for the quarter ended December 31, 2020 include:

Corporate Milestones:

Raised gross proceeds of approximately $100 million in an offering of common stock

Cardiff Oncology substantially strengthened its balance sheet in the fourth quarter, closing an underwritten public offering of 6,500,000 shares of its common stock at a public offering price of $13.50 per share, before deducting underwriter discounts and commissions and estimated offering expenses. The underwriters also exercised an option to purchase an additional 975,000 shares at the public offering price (less the underwriting discounts and commissions). The Company intends to use the net proceeds from this offering for clinical development of onvansertib, working capital and for other general corporate purposes.

Appointed Dr. Rodney Markin as Chairman of the Board

Prior to being appointed Chairman, Dr. Markin previously served as a Director on Cardiff’s Board from February 2014 to December 2020. He has extensive medical expertise and experience in institutional healthcare, and is currently the Vice President for Network Development, Nebraska Medicine and Associate Vice Chancellor for Business and Executive Director of the UNeTech Institute at the University of Nebraska Medical Center. In addition to currently holding several other distinguished positions in academia, Dr. Markin also has served on the boards of Perceptimed Inc. since 2014, MikroScan Technologies Inc. since 2015, Afaxys Inc. since 2017 and Paradigm Diagnostics Inc. since 2018.

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Identified a biomarker associated with onvansertib-abiraterone synergy that is enriched in mCRPC patients with the clinically defined basal molecular tumor subtype

Collaborative studies with the Massachusetts Institute of Technology and Decipher Biosciences identified a gene signature (biomarker) related to cell division pathways that can be used to predict which cancer cells will show a synergistic anti-tumor response to treatment with onvansertib in combination with abiraterone. This gene signature is correlated with the clinically defined basal molecular subtype of mCRPC, suggesting that patients with this tumor subtype may be more likely to respond to onvansertib-abiraterone combination therapy. These studies were featured in an electronic poster at the 27th Annual Prostate Cancer Foundation Scientific Retreat.

Acute Myeloid Leukemia (AML) Program:

Presented data at ASH (Free ASH Whitepaper) demonstrating the safety and anti-leukemic activity of onvansertib in relapsed/refractory AML

Updated data from a Phase 1b/2 clinical trial evaluating onvansertib in combination with decitabine in relapsed/refractory AML patients were featured in a virtual oral poster presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. These data demonstrated the safety, tolerability and anti-leukemic activity of the onvansertib-decitabine combination and showed an over-representation of splicing factor mutations in patients achieving a complete response. Additional highlights from the presentation included:

9 of 45 (20%) evaluated patients achieved a complete remission with or without hematologic count recovery (CR/CRi – 5 in Phase 1b and 4 in Phase 2)
55% of responders had a mutation in a splicing factor
2 patients proceeded to transplant following CR and 3 patients had ongoing responses as of the ASH (Free ASH Whitepaper) data cutoff
4 patients have achieved a durable response (≥9 months) – as of data cut-off date
Decreases in mutant circulating tumor DNA (ctDNA) within the first treatment cycle appeared to be highly correlated with clinical response; 7 of 7 (100%) patients with CR/CRi showed a decrease in mutant ctDNA after one cycle of treatment, while only 2 of 15 (13%) non-responders showed a similar decrease
Data demonstrated that onvansertib in combination with decitabine is a safe and well-tolerated treatment regimen
Highlights for the period subsequent to the quarter end include:

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced updated data from its Phase 1b/2 trial evaluating onvansertib plus FOLFIRI (irinotecan and 5-FU)/bevacizumab in second line KRAS-mutated mCRC patients and initial findings from its Expanded Access Program (EAP)

In conjunction with the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI), Cardiff Oncology announced updated Phase 1b data demonstrating the clinical benefit of onvansertib in KRAS-mutated mCRC, as well as initial findings from its EAP. Data highlights from the Phase 1b trial, as of January 6, 2021, include:

12 of 14 (86%) evaluable patients achieved a clinical benefit (SD – stable disease plus PR – partial response)
5 of 14 (36%) evaluable patients achieved a PR; 4 patients had a confirmed PR; 1 patient went on to have curative surgery; 1 patient with a non-confirmed PR went off study following PR due to a treatment-unrelated AE
3 patients with SD remain on treatment, including 2 who have yet to have their 16-week (second) scan; time to achieving a PR ranges from 2 to 6 months in trial participants on treatment
Clinical responses were observed across different KRAS variants, including the 3 most common in colorectal cancer
Patients achieving a PR or SD showed the greatest decrease in plasma mutant KRAS after one cycle of therapy
The combination of onvansertib and FOLFIRI/bevacizumab was well tolerated
Enrollment of patients in the Phase 1b segment of the trial is complete and the recommended Phase 2 dose of onvansertib has been confirmed at 15 mg/m2. The Phase 2 segment of the trial is open to full enrollment of approximately 26 patients across 6 trial sites: USC Norris Comprehensive Cancer Center, Mayo Clinic Cancer Centers (Arizona, Rochester, Jacksonville), Kansas University Medical Center and CARTI Cancer Center.

In the EAP, Cardiff Oncology announced that 6 of the initial 9 patients treated showed tumor shrinkage and remained on treatment with durable responses lasting an average of 6 months. Notably, 5 different KRAS mutation subtypes were represented amongst these patients and most patients had received prior treatment with FOLFIRI and progressed before enrolling in the EAP.

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Announced updated Phase 2 data showing a two-fold increase in efficacy with an optimized onvansertib dosing schedule

Updated data from a Phase 2 trial evaluating the all-oral combination of onvansertib, abiraterone and prednisone in patients showing initial abiraterone resistance were featured in a virtual oral poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO-GU). These data showed that increasing the number of days of treatment with onvansertib from 5 to 14 in a 21-day cycle was associated with a greater than two-fold increase (29% to 63%) in disease control rate (DCR) at 12 weeks, the trial’s primary efficacy endpoint. Across all cohorts, the DCR at 12 weeks is 35% (13/37), indicating the trial is on track to meet the stated criteria for success on its primary efficacy endpoint (30% DCR at 12 weeks). Additional highlights from the presentation included:

The optimized dosing schedule of cohort C shows a greater than two-fold improvement in disease control rate compared to cohorts A and B
o 63% (5/8) of cohort C patients achieved the primary efficacy endpoint compared to 29% (5/17) and 25% (3/12) of cohort A and B patients, respectively
75% (6/8) of evaluable patients in cohort C had radiographic stable disease (SD) at 12 weeks, compared to 53% (9/17) in cohort A, 42% (5/12) in cohort B and 54% (20/37) across all cohorts
All cohort C patients achieving the primary efficacy endpoint remain on treatment
Data show that the combination of onvansertib and abiraterone is well tolerated across the three different dosing schedules of cohorts A-C:
Cohort A: 24 mg/m2 onvansertib on Days 1-5 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort B: 18 mg/m2 onvansertib on Days 1-5 of 14-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Cohort C: 12 mg/m2 onvansertib on Days 1-14 of 21-day cycles, plus abiraterone and prednisone beginning on Day 1 and continuing uninterrupted throughout each cycle
Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) Program:

Received "Study May Proceed" letter from the U.S. Food and Drug Administration (FDA) to begin a Phase 2 trial of onvansertib in metastatic PDAC

The Phase 2 clinical trial of onvansertib in metastatic PDAC is designed to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onyvide), leucovorin and fluorouracil (5-FU) as a second-line treatment in patients with metastatic PDAC who have failed first-line gemcitabine-based therapy. Onvansertib’s potential in PDAC, where ~95% of patients have a KRAS mutation, is supported by the promising clinical data seen in the KRAS-mutated mCRC trial evaluating onvansertib in combination with irinotecan and 5-FU (FOLFIRI). Initiation of the Phase 2 trial is expected in the first half of 2021.

Fourth Quarter Financial Results:

As of December 31, 2020, Cardiff Oncology had approximately $131 million in cash and cash equivalents.

Net cash used in operating activities in the fourth quarter of 2020 was $5.1 million, an increase of $1.8 million from $3.3 million for the same period in 2019. The increase is attributed mainly to outside services and professional fees, facilities and other and changes in operating assets and liabilities.

Research and development expenses increased by approximately $0.3 million to $3.2 million for the three months ended December 31, 2020, from $2.9 million for the same period in 2019. The increase in research and development expenses was primarily due to the increased outside service costs and clinical studies for advancing the development of our drug candidate, onvansertib. We expect increases in research and development costs to continue as we advance the onvansertib clinical development programs.

Selling, general and administrative expenses increased by approximately $1.9 million to $3.4 million for the three months ended December 31, 2020, from $1.5 million for the same period in 2019. The increase is primarily due to a one time increase in stock compensation expense, and outside services and professional fees.