aTyr Pharma Announces Fourth Quarter and Full Year 2021 Results and Provides Corporate Update

On March 14, 2022 aTyr Pharma, Inc. (Nasdaq: LIFE), a biotherapeutics company engaged in the discovery and development of innovative medicines based on novel biological pathways, reported fourth quarter and full year 2021 results and provided a corporate update (Press release, aTyr Pharma, MAR 14, 2022, View Source [SID1234610121]).

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"2021 was a milestone year for aTyr, which culminated in clinical proof-of-concept for our lead therapeutic candidate, efzofitimod (ATYR1923), and validation for our tRNA synthetase biology platform," said Sanjay S. Shukla, M.D., M.S., President and Chief Executive Officer of aTyr. "The positive results reported from our Phase 1b/2a study of efzofitimod in pulmonary sarcoidosis, our initial interstitial lung disease (ILD) indication, suggest that this novel immunomodulator has the potential to be a transformative, disease modifying therapy for patients with this and other fibrotic lung diseases with high unmet need."

"We have carried this momentum into the start of 2022. The receipt of U.S. Food and Drug Administration (FDA) orphan drug designation for efzofitimod in sarcoidosis underscores the significant challenges faced by these patients. We have a path forward as a result of our positive End-of-Phase 2 meeting with the FDA and intend to initiate a planned registrational trial in pulmonary sarcoidosis in the third quarter of this year. We also remain on track with the IND-enabling work for ATYR2810, and we expect to initiate a Phase 1 study in cancer patients in the second half of this year. We ended 2021 with approximately $107.9 million in cash, and our strong balance sheet positions us well to advance our clinical programs and progress our pipeline in the year ahead."

Fourth Quarter 2021 and Subsequent Period Highlights

Held a Type B End-of-Phase 2 meeting with the FDA regarding the company’s lead therapeutic candidate, efzofitimod, for the treatment of pulmonary sarcoidosis. The meeting followed positive results that the company reported from a Phase 1b/2a multiple-ascending dose, placebo-controlled study of efzofitimod in 37 patients with pulmonary sarcoidosis, which demonstrated safety, tolerability and consistent dose response for efzofitimod on key efficacy endpoints and improvements compared to placebo, including measures of steroid reduction, lung function, sarcoidosis symptom measures and inflammatory biomarkers. Following the FDA’s review of the data package, including data from the nonclinical program, early clinical trials and the recently completed Phase 1b/2a study, the company will proceed with the advancement of efzofitimod. The FDA discussed endpoints detailed by the company in its proposed registrational study and prioritization of outcome measurements that would best support the evaluation of efzofitimod’s efficacy. The FDA advised the continued evaluation of multiple doses of efzofitimod in a longer duration study to establish a controlled safety database that supports the determination of the optimal dose for chronic use. The company has a path forward to initiate a planned registrational study of efzofitimod that will incorporate feedback from the FDA, and the company is proceeding with its plans to initiate this study in the third quarter of 2022.
Received FDA orphan drug designation for efzofitimod for the treatment of sarcoidosis. Orphan drug designation is granted to support the development of medicines for patients with unmet needs for disorders affecting fewer than 200,000 people in the U.S. and provides certain benefits, including the potential for seven years of market exclusivity following regulatory approval, exemption from FDA application fees and tax credits for qualified clinical trials.
Announced that the United States Adopted Names Council and the World Health Organization’s International Nonproprietary Name Expert Committee selected "efzofitimod" as the nonproprietary (generic) name for ATYR1923. Going forward, aTyr will use the name efzofitimod in place of ATYR1923.
Announced an agreement with FUJIFILM Diosynth Biotechnologies, a leading contract development and manufacturing organization for biologics, viral vaccines and viral vectors, for the manufacture of efzofitimod. FUJIFILM Diosynth Biotechnologies will support process development and scale up of efzofitimod, including the manufacture of bulk drug substance for additional clinical trials in ILD.
Had a poster accepted for presentation at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The poster, titled, "ATYR2810, a fully humanized monoclonal antibody targeting the VEGF-NRP2 pathway sensitizes highly aggressive and chemoresistant TNBC subtypes to chemotherapy," will present additional preclinical data generated for ATYR2810, the company’s lead anti-Neuropilin-2 (NRP2)/VEGF antibody and IND candidate. The company expects to initiate a phase 1 study of ATYR2810 in cancer patients in the second half of 2022.
Year Ended 2021 Financial Highlights and Cash Position

Cash & Investment Position: Cash, cash equivalents and investments as of December 31, 2021, were $107.9 million.
R&D Expenses: Research and development expenses were $23.3 million for the year ended 2021, which consisted primarily of product development costs for the efzofitimod and ATYR2810 programs. Program costs for efzofitimod included preparation for the upcoming planned registrational trial in pulmonary sarcoidosis, which included the manufacture of clinical trial material and initiation of technology transfer activities with FUJIFILM Diosynth Biotechnologies. Program costs for ATYR2810 included costs related to IND-enabling activities and the initiation of manufacturing activities with Lonza.
G&A Expenses: General and administrative expenses were $10.8 million for the year ended 2021. This included an increase in the number of employees as the company prepares for the efzofitimod planned registrational trial in pulmonary sarcoidosis and a phase 1 clinical trial of ATYR2810 in cancer.
Shares Outstanding: Common shares outstanding were 27,793,035 as of December 31, 2021.
Financial Guidance

The company expects its research and development expenses to increase in 2022 as it continues to develop efzofitimod and ATYR2810 as well as its discovery programs.
Conference Call and Webcast Details

aTyr will host a conference call and webcast today at 5:00 p.m. Eastern Time / 2:00 p.m. Pacific Time to discuss its financial results and provide a corporate update. Interested parties may access the call by dialing toll-free 844-358-9116 from the US, or 209-905-5951 internationally and using conference ID 3686825. Links to a live audio webcast and replay may be accessed on the aTyr website events page at: View Source An audio replay will be available for at least 90 days following the event.

About Efzofitimod

aTyr is developing efzofitimod as a potential therapeutic for patients with fibrotic lung disease. Efzofitimod, a fusion protein comprised of the immunomodulatory domain of histidyl-tRNA synthetase fused to the FC region of a human antibody, is a selective modulator of neuropilin-2 that downregulates innate and adaptive immune response in inflammatory disease states. aTyr’s lead indication for efzofitimod is pulmonary sarcoidosis, a major form of interstitial lung disease. Clinical proof-of-concept for efzofitimod was recently established in a Phase 1b/2a multiple-ascending dose, placebo-controlled study of efzofitimod in patients with pulmonary sarcoidosis, which demonstrated safety and a consistent dose response and trends of benefit of efzofitimod compared to placebo on key efficacy endpoints, including steroid reduction, lung function, clinical symptoms and inflammatory biomarkers. aTyr intends to initiate a planned registrational study of efzofitimod in pulmonary sarcoidosis in the third quarter of 2022.

Nutcracker Therapeutics Raises $167 Million in Series C Financing to Advance its mRNA Therapeutics and First-of-its-Kind Biochip-based Manufacturing Platform

On March 14, 2022 Nutcracker Therapeutics, Inc., a biotech company developing RNA therapeutics using its proprietary biochip-based manufacturing platform, reported it has raised $167 million in Series C financing led by ARCH Venture Partners (Press release, Nutcracker Therapeutics, MAR 14, 2022, View Source [SID1234610020]). The funds will allow the company to expand and advance its pipeline of mRNA medicines for cancer, in addition to further refining its RNA manufacturing platform and the underlying technology.

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"The recent success of the mRNA vaccines for COVID-19 has brought newfound energy around the use of RNA as a therapeutic tool," said Igor Khandros, Ph.D., co-founder, and CEO of Nutcracker Therapeutics. "As a consequence, we have an unparalleled opportunity to bring this emerging class of medicines to treat patients suffering from very complex diseases. With this significant milestone and the support of our top-flight investors and partners, we are well-positioned to begin the next phase of Nutcracker’s evolution: accelerating RNA therapeutics development within the company and beyond using our unique ‘GMP-in-a-box’ platform, and meet the rising demand for RNA therapies and their efficient, scalable manufacturing."

Nutcracker Therapeutics’ RNA manufacturing platform is at the core of the company’s therapeutic effort. It combines RNA biochemistry with microfluidic engineering, semiconductor-like biochips, and a proprietary nanoparticle delivery technology to create a fully automated and isolated manufacturing pathway. The platform is capable of supporting RNA therapeutic development from discovery to the clinic and commercialization, scaling up appropriately at each stage. Using this platform, the company aims to increase the speed and scale at which therapeutics can be discovered, developed, and manufactured.

Concurrent to the financing, Nutcracker Therapeutics has added Michael F. Bigham, former CEO and current executive chairman of the board of Paratek Pharmaceuticals, to its board of directors. Bigham has more than 30 years of leadership experience in the biopharmaceutical and life science industries, including as a general partner at Abingworth LLP, President and Chief Executive Officer of Coulter Pharmaceuticals, and in various roles at Gilead Sciences, such as Chief Financial Officer and Executive Vice President Operations.

"RNA has unique qualities as a therapeutic modality and could prove to be a first-line tool for many diseases," commented Bigham. "Nutcracker Therapeutics is well-positioned to develop RNA therapeutics in a scalable and efficient manner with its innovative platform. I’m excited to be a part of the team and help further its goal of advancing its pipeline into the clinic and bringing RNA therapies to patients with the greatest need."

Results for the 12- and 18-month periods ended 31 December 2021

On March 14, 2022 Abcam plc (Nasdaq: ABCM; AIM: ABC) (‘Abcam’, the ‘Group’ or the ‘Company’), a global leader in the supply of life science research tools, reported its final results for the 18-month period ended 31 December 2021 (the ‘period’) (Press release, Abcam, MAR 14, 2022, View Source [SID1234610040]). The Group’s accounting reference date changed from 30 June to 31 December during the year1, therefore these financial statements report on both a 12-and 18-month period.

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Excludes the amortisation of the fair value of assets relating to the inventory acquired in connection with the acquisition of BioVision.

** Adjusted figures exclude impairment of intangible assets, systems and process improvement costs, acquisition costs, amortisation of fair value adjustments, integration and reorganisation costs, amortisation of acquisition intangibles, share-based payments and employer tax contributions thereon, the tax effect of adjusting items and credits from patent box claims. Such excluded items are described as ‘adjusting items’. Further information on these items is shown in note 4 to the consolidated financial statements.

*** In previous reporting periods, share-based payments have not been included within adjusting items. With the approval of the Profitable Growth Incentive Plan (‘PGIP’) during CY2021, management considers it to be more appropriate and more consistent with its closest comparable companies to include all share-based payments in adjusting items. To aid comparison with our previous presentation of results, we have included the adjusted operating margin in the table above on a like-for-like basis, excluding this change (‘Like-for-like’).

**** Net Cash comprises cash and cash equivalents less borrowings.

CY2021 FINANCIAL HIGHLIGHTS1,2

• Revenue growth of +22% (+17% reported) at constant exchange rates, compared to CY2020, including a 1%pt contribution from the acquisition of BioVision o +38% total in-house CER revenue growth (including Custom Products & Licensing3 and £2.6m of incremental revenue from BioVision) (+32% reported) o Revenue from in-house products and services contributed 61% of total revenue (including Custom Products & Licensing3 and £2.6m of incremental revenue from BioVision)
• Adjusted2 gross margin increased by over 200 basis points to 72.2% (CY2020: 70.0%), benefiting from the contribution of higher margin in-house products and volume leverage resulting from the increase in revenue
• Adjusted2 operating profit of £60.4m (excluding share-based payments), equating to an adjusted operating margin of 19.2% (CY2020: 18.8%)
• Adjusted2 operating margin on a like-for-like4 basis improved over 300 basis points to 16.5% in H2 ’21 (JulDec), from 13.3% in H1 ’21 (Jan-Jun)
• Statutory reported operating profit inc
• Net cash inflow from operating activities increased to £62.9m (CY2020: £58.9m)

BUSINESS HIGHLIGHTS
• Focus on serving customers’ needs globally as research activity levels continued to normalise and demand for Abcam products increased
• Positive customer transactional Net Promotor Score (‘tNPS’) of +56 (CY2021) and product satisfaction rates at all-time highs
• Completed the acquisition of BioVision, Inc (‘BioVision’), a leading innovator of biochemical and cell-based assays, in October 2021, for cash consideration of $340m (on a cash free, debt free basis)
• High employee engagement, with the business ranked in the Top 5 in the Glassdoor UK Employees’ Choice Awards in January 2022, for the second year running
• Strengthened and expanded leadership in commercial and operational teams with senior hires in Commercial, Brand, China, and Supply Chain
• Expanded the Group’s global presence, with the opening of new and enlarged sites in China, the US (Massachusetts, California, Oregon), Singapore, and Australia
• Upgraded supply chain systems at three locations, implemented new data architecture, and began transition to a new e-commerce platform, with completion of the digital transformation due in 2022
• Completed the secondary US listing on Nasdaq’s Global Market in October 2020 (supplementing existing listing on AIM on the London Stock Exchange)
• Expanded Asia, digital, and life science industry experience on the Board of Directors, with the appointments of Bessie Lee, Mark Capone and Sally Crawford, as Non-Executive Directors

SHARE TRADING, LIQUIDITY AND LISTING
• Following our listing on Nasdaq in October 2020, the number of Abcam shares traded as ADSs on Nasdaq has doubled. While only 10% of our shares trade in the US market, it represents 25% of liquidity
• The Board continues to review options to increase share liquidity and intends to consult with shareholders on these options in due course

CY2022 GUIDANCE
• Global lab activity continues to recover, though some uncertainty remains
• CY2022 trading performance YTD is in line with our expectations
• Expect total CER5 revenue growth of c.20% (including BioVision) with mid-teens organic CER revenue growth
• Expect continued adjusted gross margin improvement from the contribution of higher margin in-house products and full year impact of the BioVision acquisition
• Expect total adjusted operating cost growth (including depreciation and amortisation) at mid-teens percentage, as we slow rate of investment and leverage recent investments

LONG TERM GOALS TO CY2024
• CY2024 revenue goal target range increased by £25m to £450m-£525m, adjusted to incorporate BioVision6 and current operating performance
• Adjusted operating margin and ROCE targets remain unchanged Commenting on today’s results, Alan Hirzel, Abcam’s Chief Executive Officer, said: "I am grateful to everyone at Abcam for their dedicated effort through this most challenging time and thank our customers and partners for their ongoing trust and support. We have had another successful year operationally and financially despite the ongoing challenges. As we look ahead to 2022, we expect to create more innovation and success out of the past two years of investment as we installed elements of Abcam’s long term growth strategy.

The scientific community remains our guide and with their support we are becoming a more influential and trusted brand globally." Analyst and investor meeting and webcast: Abcam will host a conference call and webcast for analysts and investors today at 13:00 GMT/ 09:00 EDT. For details, and to register, please visit corporate.abcam.com/investors/reports-presentations A recording of the webcast will be made available on Abcam’s website, corporate.abcam.com/investors

2. These results include discussion of alternative performance measures which include revenues calculated at Constant Exchange Rates (CER) and adjusted financial measures. CER results are calculated by applying prior period’s actual exchange rates to this period’s results. Adjusted financial measures are explained in note 2 and reconciled to the most directly comparable measure prepared in accordance with IFRS in note 4 to the interim financial statements.

3. Custom Products & Licensing (CP&L) revenue comprises custom service revenue, revenue from the supply of IVD products and royalty and licence income.

4. In previous reporting periods, share-based payments have not been included within adjusting items. With the approval of the Profitable Growth Incentive Plan (‘PGIP’) during CY2021, management considers it to be more appropriate and more consistent with its closest comparable companies to include all share-based payments in adjusting items. To aid comparison with our previous presentation of results, we also calculate adjusted operating margin on a like-for-like basis, excluding this change (‘Like-for-like’).

5. Average CY2021 exchange rates to GBP as follows: USD: 1.378; EUR: 1.159, RMB: 8.891, JPY: 150.7 6. Last 12-month BioVision recurring revenues of £17.8m at point of acquisition, adjusted for non-recurring COVID-19 related revenues, and sales to Abcam during that period. The information communicated in this announcement contains inside information for the purposes of Article 7 of the Market Abuse Regulation (EU) No. 596/2014. This announcement shall not constitute an offer to sell or solicitation of an offer to buy any securities. This announcement is not an offer of securities for sale in the United States, and the securities referred to herein may not be offered or sold in the United States absent registration except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the U.S. Securities Act of 1933, as amended. Any public offering of such securities to be made in the United States will be made by means of a prospectus that may be obtained from the issuer, which would contain detailed information about the company and management, as well as financial statements.

Dialectic Therapeutics Announces DT2216 Has Received Orphan Drug Designation from the FDA for the Treatment of T-Cell Lymphoma

On March 14, 2022 Dialectic Therapeutics, Inc. (Dialectic), a Texas-based clinical stage biotechnology company focused on creating innovative new technologies to treat cancer, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to DT2216 for the treatment of T-cell lymphoma (Press release, Dialectic Therapeutics, MAR 14, 2022, View Source [SID1234610056]). DT2216 is Dialectic’s first generation compound built using its proprietary and novel Antiapoptotic Protein Targeted Degradation (APTaD) technology platform.

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"This is an important milestone in the development of DT2216, our lead APTaD compound. The FDA’s decision to grant orphan drug designation underscores our belief that DT2216 could be a promising therapeutic for T-cell lymphoma patients" said Dr. David Genecov, Dialectic’s President and Chief Executive Officer. "There is a critical unmet need for people diagnosed with this rare cancer, in which current approved therapies have relatively low response rates".

Normal T-cells require BCL-XL expression to survive thymic selection during their development. After thymic selection BCL-XL normal T-cells no longer express BCL-XL. However, many T-cell lymphomas re-express BCL-XL as a mechanism of their neoplastic transformation and permits their continued survival as a malignancy. Studies have demonstrated the importance of BCL-XL in T-cell lymphoma survival. Dialectic has shown that DT2216 is an effective treatment for T-cell lymphoma in preclinical studies.

The FDA’s Office of Orphan Products Development grants orphan designation status to drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases, or conditions that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain benefits, including financial incentives to support clinical development and the potential for up to seven years of market exclusivity in the U.S. upon regulatory approval.

About DT2216 and the APTaD Technology Platform
DT2216 is currently being investigated in a Phase 1 clinical trial designed as an open-label, first-in-human, dose escalation study in patients with histologically or cytologically confirmed advanced or metastatic solid tumors and hematologic malignancies who are no longer responsive to approved or accepted standard-of-care interventions. Patients in the Phase 1 trial will receive a single intravenous (IV) infusion of DT2216 twice weekly for at least 4 weeks, with each cycle consisting of 28 days. Additional information about the clinical trial is available at ClinicalTrials.gov (NCT04886622).

In preclinical studies DT2216 selectively induces the degradation of B-cell lymphoma extra-large, or BCL-XL, in cancer cells and either stimulates the return of cellular apoptosis or sensitizes the cells to be more susceptible to chemotherapy, and thus cellular destruction. DT2216 has been shown to be effective in various in vitro models of hematologic and solid tumors as a single agent and in combination with other chemotherapeutic agents. Further, these preclinical studies show cancer cells are less likely to develop resistance to DT2216 compared to other chemotherapy drugs. DT2216 accomplishes this with less impact on platelets.

As with BCL-XL, there are many other significant proteins associated with cancer that cannot be targeted with current therapies. Our proprietary APTaD technology platform is a novel approach that can be applied to the broader BCL family and other protein targets. Our current research and preclinical efforts are focused on developing next generation APTaD candidates to address this high unmet need.

Lantern Pharma to Present Positive Preclinical Data on the Effectiveness of LP-184 in Brain Metastases at the American Association of Cancer Research (AACR) Annual Meeting

On March 14, 2022 Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR artificial intelligence ("A.I.") and machine learning (ML) platform to transform the cost, pace, and timeline of oncology drug discovery and development, reported that it will present positive preclinical data on the in vitro efficacy of its drug candidate LP-184 in brain metastases (mets) at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting, April 8-13th, 2022, held in New Orleans, Louisiana (Press release, Lantern Pharma, MAR 14, 2022, View Source [SID1234610021]).

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LP-184 is a small molecule drug candidate and next generation acylfulvene that preferentially damages DNA in cancer cells that overexpress certain biomarkers and is therefore lethal in tumors that harbor mutations or deficiencies in DNA repair pathways. LP-184 has already been demonstrated preclinically to have potent efficacy in several targeted central nervous system (CNS) cancer indications, including glioblastoma multiforme (GBM) and atypical teratoid rhomboid tumors (ATRT). The development promise for LP-184 in these indications is strengthened by LP-184’s favorable blood brain barrier (BBB) permeability. LP-184 has also demonstrated potent tumor cell killing capabilities in vitro and in animal xenografts of tumors such as lung, breast, melanoma and colon, many of which frequently metastasize to the brain. The tumor specificity of LP-184 is driven by expression levels of PTGR1, and Lantern’s RADR analysis indicates that such expression levels are retained in brain mets of these primary tumors.

The virtual poster will be presented by Lantern Pharma in collaboration with Johns Hopkins School of Medicine and the Kennedy Krieger Institute and will describe positive preclinical data demonstrating the effectiveness of LP-184 treatment in brain mets cell models derived from patient lung, skin, and breast cancers. The poster will also show that in an in vitro model of brain mets from lung cancer, LP-184 treatment was found to be 6 times more potent than EGFR tyrosine kinase inhibitors (a widely used type of therapy).

Brain mets are more common than primary brain tumors (cancer that starts in the brain), and studies suggest that brain mets occur in about 10%-30% of patients with cancer. In the U.S., brain mets (from all cancers combined) are estimated to account for over 100,000 diagnoses annually and generally have a very poor prognosis even after radiation therapy. There is an urgent and unmet clinical need for novel therapies for brain mets due to a current lack of novel agents that can cross the blood brain barrier. LP-184’s favorable BBB permeability paired with its observed preclinical efficacy in certain CNS cancers, underscore its potential to become a vital treatment option for patients relapsed from current standard of care treatment or for use in combination with other agents.

LP-184 was recently granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of malignant gliomas, pancreatic cancer, and ATRT, and was also granted a Rare Pediatric Disease Designation for ATRT. These designations and continued positive preclinical data will help to accelerate LP-184 towards IND submission and multiple Phase 1 clinical trials in 2022.

Details of the virtual poster presentation are listed below or can be found on the AACR (Free AACR Whitepaper) website:

Title: LP-184, a tumor site activated small molecule synthetic lethal therapeutic, is effective in central nervous system cancers
Permanent Abstract number: 5442
Date and Time: April 8, 2022, 12:00pm-1:00pm CST
Session Category: Experimental and Molecular Therapeutics
Session Title: Small Molecule Therapeutic Agents
Presenter: Aditya Kulkarni, Ph.D., Lantern Pharma