Maplirpacept

Pictured: Pacman, representing the “don’t eat me” signal broadcasted by CD47/iStock, artisteer Companies researching CD47 inhibitors can’t seem to catch a break. Gilead’s multibillion-dollar bet on the CD47-targeting antibody therapy magrolimab appears in jeopardy, and AbbVie recently ended its collaboration with I-Mab, the maker of another anti-CD47 drug, after terminating two early-phase studies of the candidate last August. What once seemed like a competitive field has thinned out considerably, leading some insiders to speculate that CD47 antibodies may be fatally flawed as a therapeutic class. But there is a glimmer of hope. Earlier this month, Bay Area–based ALX Oncology announced positive interim data from a Phase II trial of evorpacept in HER2-positive gastric cancer, bucking the recent downturns across the field. This positive readout, coupled with ALX’s concurrent announcement that it will move into a Phase III trial in the second half of 2024, underscores that the story of anti-CD47 therapies is still being written, said ALX CEO Jason Lettmann. Jason Lettmann “Like most areas of biotech, there's all sorts of ups and downs, but this one has more than its fair share of incredible highs and moments of a lot of doubt,” Lettmann told BioSpace. Still, a fundamental question remains: Why haven’t efforts by some of biotech’s biggest names translated into effective therapeutics? Experts told BioSpace that the apparent setbacks can be attributed to known safety concerns for anti-CD47 antibodies combined with an under-diversified field with too many drugs going after the same target. Even so, they remain hopeful that a CD47-targeting drug can make it to market. Toxic Contradictions CD47 is a transmembrane protein expressed in many human cells, including red blood cells, platelets and immune cells, as well as in a wide variety of cancer cells. The reason cancer cells express this protein is clear: when it binds to its receptor, CD47 inhibits the innate immune system by broadcasting a “don’t eat me” signal. In the past decade, researchers have engineered antibodies to decrease this signal in cancer cells and, in some cases, provide an unambiguous “eat me” signal to macrophages. But these antibody drug candidates often have off-target effects, said Laurence Blumberg, a biotech executive who was formerly the CEO of Arch Oncology, which shuttered earlier this year despite receiving the FDA’s Orphan Drug Designation for its anti-CD47 antibody. Laurence Blumberg “The problem is that CD47 is broadly expressed in normal cells and particularly broadly expressed in components of blood—platelets, white blood cells, red blood cells—and the big issue has been the safety and toxicity of all the different molecules,” Blumberg told BioSpace. “We haven’t gotten to the point where the efficacy has been compelling enough to justify arguably life-threatening toxicities.” Blumberg said these toxicities vary depending on the type of anti-CD47 drug. Monoclonal antibodies, for example, are often associated with conditions such as anemia and thrombocytopenia. This is because the antibodies bind to CD47 on healthy blood cells as well as cancer cells and induce macrophages to engulf and digest both the healthy and diseased cells. Indeed, safety concerns have plagued Gilead’s magrolimab. In January 2022, the FDA placed a hold on trials of the candidate, which was being tested in multiple studies in combination with azacitidine, due to “an apparent imbalance” in suspected unexpected serious adverse reactions. The hold was lifted several months later, but the FDA issued a second partial clinical hold on magrolimab in acute myeloid leukemia (AML) in August. Additionally, a Phase Ib study found that 28.7% of AML patients treated with magrolimab plus azacitidine developed anemia related to the anti-CD47 drug. Gilead has also paused or discontinued multiple clinical trials of magrolimab in recent months. “The efficacy data has been tantalizing,” Blumberg said, “but not really robust enough in light of the fact that you’re dealing with a drug class that is fraught with toxicity risks, and all the molecules have a nuanced toxicity. I don’t think it’s over for the class, but I do think that there’s headwind.” A Field in Flux Prior to the spate of disappointing results, the funding landscape for anti-CD47 immunotherapies looked rosy, buoyed by two multibillion-dollar acquisitions. In March 2020, Gilead acquired magrolimab’s manufacturer, Forty Seven, for $4.9 billion. Soon after, AbbVie entered into its agreement with I-Mab, and Pfizer purchased Trillium Therapeutics, the maker of two anti-CD47 proteins, for $2.22 billion. The acquisitions that occurred alongside promising preclinical and clinical results resulted in the field being flooded with “a lot of money to chase maybe too many drugs going after the same target,” Blumberg said. “But there was nothing wrong with the pursuit.” Some, like Lettmann, believe that many drugmakers unknowingly kneecapped their anti-CD47 antibody therapies by coupling the inhibition of the “don’t eat me” signal with the promotion of the “eat me” signal. “If you try to accomplish both as part of the same molecule, it will be very difficult to effectively target cancer over healthy [cells],” Lettmann said. Magrolimab’s makers tried to skirt the issue by switching from one subclass of immunoglobulin G to another, he continued. Pfizer has similarly stuck to this subclass. In a statement, a Pfizer spokesperson told BioSpace that its anti-CD47 candidate maplirpacept has demonstrated minimal red blood cell binding and few reported cases of anemia. Maplirpacept acts on both cancer cells and macrophages, the spokesperson said, and has demonstrated “encouraging activity” when used as a monotherapy in studies with more than 75 patients. Currently, the company is conducting Phase I and II trials in ovarian cancer, multiple myeloma and diffuse large B-cell lymphoma. ALX has approached drug development with safety in mind, Lettmann said. Evorpacept decouples anti-CD47 monoclonal antibodies’ two mechanisms of action, blocking the cancer cells’ “don’t eat me” signal without turning macrophages into indiscriminate killers—an approach that, when combined with other cancer therapies, has shown preclinical and clinical promise. This month, ALX reported that 52% of patients with gastric/gastroesophageal junction (GEJ) cancer enrolled in a Phase II trial responded to a combination of evorpacept and trastuzumab, ramucirumab and paclitaxel, compared to 22% of patients who received only the three latter drugs. ALX plans to report a final analysis from the trial next year, along with a half-dozen readouts from trials of evorpacept in combination with chemotherapy, a checkpoint inhibitor and an antibody-drug conjugate. Even so, ALX’s journey has not been without its bumps as the company recently axed CD47 programs where evorpacept attempted to treat myelodysplastic syndrome and acute myeloid leukemia—though Lettmann clarified that the mechanism tested in the two blood cancers differs from evorpacept’s mechanism of action in solid tumors. For Lettmann, winning FDA approval for evorpacept would be the culmination of a nine-year journey for ALX and its leadership. Contingent on positive final results from the Phase II trial and the commencement next year of a Phase III trial for gastric/GEJ cancer, Lettmann said he believes the company has “a very logical path to an approval” in this indication. Maddie Bender is a freelance science journalist based in Honolulu, HI. You can contact her through her website, maddiebender.com.

– Monjuvi® U.S. net product sales of US$ 23.3 million (€ 21.7 million) for the second quarter 2022, a 25% Q-Q growth and 29% Y-Y growth – Efficacy and safety data of pelabresib for potential treatment improvement in myelofibrosis presented at EHA Congress 2022 – Entered into collaboration with Pfizer and Incyte for a combination study of Monjuvi and TTI-622, a Fusion Protein Directed Against CD47 – Updated financial guidance published on July 26, 2022 PLANEGG/MUNICH, Germany--(BUSINESS WIRE)-- Conference call and webcast (in English) tomorrow, August 4, 2022, at 2:00pm CEST (1pm BST/8:00am EDT) MorphoSys AG (FSE: MOR; NASDAQ: MOR) reports results for the second quarter and first half year of 2022. “In the second quarter of 2022 we made important progress in advancing patient enrollment across our pivotal phase 3 studies and commercializing Monjuvi, where we observed a bounce back in sales following a challenging first quarter”, said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. “Despite the reduced guidance update, we anticipate Monjuvi growth to continue into the second half of the year and beyond. We remain well capitalized to get through important clinical milestones, potentially bringing new effective blood cancer medicines to patients and generating significant value for our shareholders.” Tafasitamab Highlights: Monjuvi (tafasitamab-cxix) U.S. net product sales of US$ 23.3 million (€ 21.7 million) for the second quarter 2022 (Q2 2021: US$ 18.0 million (€ 14.9 million)) and US$ 41.9 million (€ 38.3 million) for the first half of 2022. Minjuvi® royalty revenue of € 0.7 million for sales outside of the U.S. in the second quarter 2022 and € 1.4 million for the first half of 2022. Pfizer, Incyte and MorphoSys signed a clinical trial collaboration and supply agreement on June 13, 2022, to investigate the immunotherapeutic combination of Pfizer’s TTI-622, a novel SIRPα-Fc fusion protein, and Monjuvi plus lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT). Other highlights: Pelabresib data presented at EHA Congress 2022: Efficacy and safety data from the ongoing phase 2 MANIFEST trial of pelabresib in myelofibrosis and translational research findings suggesting the potential disease-modifying effect of pelabresib in patients with myelofibrosis were presented in oral presentations at the European Hematology Association 2022 (EHA 2022) Hybrid Congress. Agreement with HIBio on felzartamab and MOR210: Human Immunology Biosciences, Inc. (HIBio) signed an equity participation agreement and license agreements with MorphoSys to allow HIBio to develop and commercialize MorphoSys’ felzartamab, an anti-CD38 antibody, and MOR210, an anti-C5aR1 antibody across all indications worldwide, with the exception of Greater China for felzartamab and Greater China and South Korea for MOR210. As part of the agreements, MorphoSys will receive a 15% equity stake in HIBio, along with certain equity earn-in provisions and standard investment rights. On achievement of development, regulatory and commercial milestones, MorphoSys will be eligible to receive payments from HIBio of up to US$ 1 billion across both programs, in addition to tiered, single- to low double-digit royalties on net sales of felzartamab and MOR210. Upon signing, MorphoSys also received an upfront payment of US$ 15 million for MOR210. HIBio has full responsibility for future development and commercialization of felzartamab and MorphoSys will transfer the development candidate and the clinical studies over to HIBio in the next months. MorphoSys will be compensated for ongoing program expenses for felzartamab during this program transition period by HIBio. Significant Events After the End of the Second Quarter of 2022: On July 26, 2022, MorphoSys notified Royalty Pharma that it intends to draw US$ 300.0 million (€ 296.3 million) of the development funding bond. The proceeds are anticipated to be delivered to MorphoSys in September 2022 and will be used primarily to fund development activities. Financial Results for the Second Quarter of 2022 (IFRS): Revenues for the second quarter 2022 were € 59.4 million compared to € 38.2 million for the same period in 2021. The year-over-year growth in Monjuvi product sales was driven by higher demand. in € million* Q2 2022 Q1 2022 Q2 2021 Q-Q Δ Y-Y Δ Revenues 59.4 41.5 38.2 43 % 55 % Monjuvi product sales 21.7 16.6 14.9 31 % 46 % Royalties 22.0 19.0 13.7 16 % 61 % Licenses, milestones and other 15.7 5.8 9.6 > 100% 64 % * Differences due to rounding. Cost of Sales: In the second quarter 2022, cost of sales were € 17.2 million compared to € 10.1 million for the comparable period in 2021. Research and Development (R&D) Expenses: In the second quarter 2022, R&D expenses were € 60.9 million compared to € 40.5 million in the second quarter 2021. The increase in R&D expenses is primarily due to the first-time inclusion of Research and Development expenses from Constellation from July 2021 on and higher investment to support the advancement of clinical programs. Selling, General and Administrative (SG&A) Expenses: Selling expenses in the second quarter 2022 were € 24.0 million compared to € 28.5 million in the second quarter 2021. The decrease was driven by higher investments in 2021 made into the commercial organization, the first full year after the Monjuvi launch. General and administrative (G&A) expenses in the second quarter 2022 amounted to € 12.4 million compared to € 30.5 million in the second quarter 2021. The decrease was driven by the transaction costs for the Constellation acquisition and Royalty Pharma agreements executed in the second quarter 2021. Operating Loss: Operating loss amounted to € 55.1 million in the second quarter 2022 (Q2 2021: operating loss of € 71.4 million). Consolidated Net Loss: For the second quarter 2022, consolidated net loss was € 235.0 million (Q2 2021: consolidated net profit of € 20.9 million). Financial Results for the first six months 2022 (IFRS): Revenues for the first six months of 2022 were € 100.9 million (H1 2021: € 85.4 million). Revenues include € 38.3 million from the recognition of Monjuvi product sales in the U.S. Royalties in H1 2022 included € 1.4 million from the sale of Minjuvi outside of the U.S. by our partner Incyte and € 39.7 million from Tremfya® sales which is fully passed onto Royalty Pharma. in € million* H1 2022 H1 2021 Y-Y Δ Revenues 100.9 85.4 18 % Monjuvi product sales 38.3 27.8 38 % Royalties 41.0 25.4 61 % Licenses, milestones and other 21.5 32.3 (33) % * Differences due to rounding. Cost of Sales: For the first six months of 2022, cost of sales were € 25.1 million (H1 2021: € 15.2 million). The year-over-year increase was primarily driven by higher sales of Monjuvi in the U.S. and Minjuvi outside of the U.S. R&D Expenses: In the first six months of 2022, R&D expenses were € 126.0 million compared to € 73.8 million for the same period in 2021. The R&D expenses increased due to inclusion of expenses from Constellation and higher investments to support the advancement of clinical programs. SG&A Expenses: Selling expenses decreased in the first six months of 2022 to € 45.9 million compared to € 56.6 million for the same period in 2021. The year-over-year decrease was primarily driven by higher investments made in the commercial organization in 2021, the first full year after the Monjuvi launch. G&A expenses amounted to € 27.0 million in the first six months of 2022 compared to € 40.8 million for the same period in 2021. The year-over-year decrease was driven primarily by the transaction costs for the Constellation acquisition and Royalty Pharma agreements executed in the second quarter of 2021. Operating Loss: Operating loss amounted to € 123.1 million in the first six months of 2022 (H1 2021: operating loss of € 101.0 million). Consolidated Net Profit / Loss: For the first six months of 2022, consolidated net loss was € 357.6 million (H1 2021: consolidated net loss of € 20.7 million). Cash and Other Financial Assets: As of June 30, 2022, the Company had cash and other financial assets of € 754.3 million compared to € 976.9 million on December 31, 2021. The Company anticipates proceeds of US$ 300.0 million in September 2022 from the development funding bond provided by Royalty Pharma. Number of shares: The number of shares issued totaled 34,231,943 on June 30, 2022, remained unchanged since December 31, 2021. Updated Full Year 2022 Financial Guidance: The updated financial guidance was issued on July 26, 2022. Amounts in million Updated 2022 Financial Guidance Previous* 2022 Financial Guidance 2022 Guidance Insights Monjuvi U.S. Net Product Sales US$ 90m to 110m US$ 110m to 135m 100% of Monjuvi U.S. product sales are recorded on MorphoSys’ income statement and related profit/loss is split 50/50 between MorphoSys and Incyte. Gross Margin for Monjuvi U.S. Net Product Sales 75% to 80% 75% to 80% 100% of Monjuvi U.S. product cost of sales are recorded on MorphoSys’ income statement and related profit/loss is split 50/50 between MorphoSys and Incyte. R&D expenses € 275m to 300m € 300m to 325m Reduction in guidance range driven primarily by license agreement for felzartamab to HIBio executed on June 14, 2022. SG&A expenses € 150m to 165m € 155m to 170m 53% to 58% of mid-point of SG&A expenses represent Monjuvi U.S. selling costs of which 100% are recorded in MorphoSys’ income statement. Incyte reimburses MorphoSys for half of these selling expenses. *The Previous 2022 Financial Guidance was initially provided on January 7 and reiterated on March 16 and on May 4, 2022. Additional information related to 2022 Financial Guidance: Tremfya royalties will continue to be recorded as revenue without any cost of sales in MorphoSys’ income statement. These royalties, however, will not contribute any cash to MorphoSys as 100% of the royalties will be passed on to Royalty Pharma. MorphoSys anticipates receiving royalties for Minjuvi sales outside of the U.S. Guidance for these royalties is not being provided as MorphoSys does not receive any sales forecasts from its partner Incyte. MorphoSys does not anticipate any significant cash-accretive revenues from the achievement of milestones in 2022. Milestones for otilimab are passed on to Royalty Pharma. Milestones from all other programs remain with MorphoSys at 100%. MorphoSys anticipates sales of commercial and clinical supply of tafasitamab outside of the U.S. to its partner Incyte. Revenue from this supply is recorded in the “Licenses, milestones and other” category in MorphoSys’ income statement. These sales result in a zero gross profit/margin. As such, MorphoSys does not provide guidance for these sales. While R&D expense is anticipated to grow year-over-year due to investments in three pivotal studies, the growth is partially being offset by the consolidation of research/discovery activities. SG&A expense guidance range reflects savings from synergies following the acquisition of Constellation and streamlined commercialization efforts. Operational Outlook for 2022: MorphoSys anticipates the following key development milestones in 2022: First proof-of-concept data from the ongoing clinical phase 2 study of CPI-0209 in solid tumors and blood cancer; MorphoSys’ partner Roche expects a pivotal data readout of the GRADUATE 1 and GRADUATE 2 trials with gantenerumab in the second half of 2022. Roche initiated these phase 3 development programs for patients with Alzheimer’s disease in 2018; MorphoSys’ partner GSK expects a pivotal data readout of the phase 3 ContRAst program investigating otilimab for rheumatoid arthritis by the end of 2022. MorphoSys Group Key Figures (IFRS, end of the second quarter: June 30, 2022) in € million H1 2022 H1 2021 Δ Q2 2022 Q2 2021 Δ Revenues 100.9 85.4 18 % 59.4 38.2 55 % Product Sales 38.3 27.8 38 % 21.7 14.9 46 % Royalties 41.0 25.4 61 % 22.0 13.7 61 % Licenses, milestones and other 21.5 32.3 (33) % 15.7 9.6 64 % Cost of Sales (25.1) (15.2) 65 % (17.2) (10.1) 70 % Gross Profit 75.8 70.2 8 % 42.2 28.1 50 % Total Operating Expenses (198.8) (171.2) 16 % (97.3) (99.5) (2) % Research and Development (126.0) (73.8) 71 % (60.9) (40.5) 50 % Selling (45.9) (56.6) (19) % (24.0) (28.5) (16) % General and Administrative (27.0) (40.8) (34) % (12.4) (30.5) (59) % Operating Profit / (Loss) (123.1) (101.0) 22 % (55.1) (71.4) (23) % Other Income 9.2 2.8 >100% 7.8 1.7 >100% Other Expenses (15.5) (3.4) >100% (11.8) (1.4) >100% Finance Income 16.7 116.3 (86) % 6.2 102.4 (94) % Finance Expenses (248.0) (36.8) >100% (185.1) 2.9 >(100)% Income from Reversals of Impairment Losses / (Impairment Losses) on Financial Assets (1.0) 0.3 >(100)% (1.0) 0.2 >(100)% Income Tax Benefit / (Expenses) 4.0 1.0 >100% 4.0 (13.5) >(100)% Consolidated Net Profit / (Loss) (357.6) (20.7) >100% (235.0) 20.9 >(100)% Earnings per Share, Basic and Diluted (10.47) (0.63) >100% (6.88) — — Earnings per Share, Basic — — — — 0.64 — Earnings per Share, Diluted — — — — 0.61 — Cash and other financial assets (end of period) 754.3 976.9 * (23) % 754.3 976.9 * (23) % *Value as of December 31, 2021 MorphoSys will hold its conference call and webcast on August 4, 2022, to present the results of the second quarter and first half of 2022 and the outlook for 2022. Dial-in number for the conference call (in English) at 2:00pm CEST; 1:00pm BST; 8:00am EDT: Germany: +49 (0)69 22222 5197 UK: +44 (0)330 165 4012 USA: +1 646 828 8073 Confirmation Code: 6282828 Please dial in 10 minutes before the beginning of the conference. A live webcast and slides will be made available at the Investors section under "Upcoming Events & Conferences" on MorphoSys' website, and after the call, a slide-synchronized audio replay of the conference will be available at the same location. The statement for the second quarter/first half year of 2022 (IFRS) are available for download at: About MorphoSys At MorphoSys, we are driven by our mission: More life for people with cancer. As a global commercial-stage biopharmaceutical company, we use groundbreaking science and technologies to discover, develop, and deliver innovative cancer medicines to patients. MorphoSys is headquartered in Planegg, Germany, and has its U.S. operations anchored in Boston, Massachusetts. To learn more, visit us at and follow us on Twitter and LinkedIn. About Monjuvi Monjuvi® (tafasitamab-cxix) is a humanized Fc-modified CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb® engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP). In the United States, Monjuvi® (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). In Europe, Minjuvi® (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT). Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials. Monjuvi® and Minjuvi® are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name MONJUVI® in the U.S., and marketed by Incyte under the brand name Minjuvi® in Europe, the UK and Canada. XmAb® is a registered trademark of Xencor, Inc. Tremfya® is a registered trademark of Janssen Biotech, Inc Forward Looking Statements This communication contains certain forward-looking statements concerning the MorphoSys group of companies. The forward-looking statements contained herein represent the judgment of MorphoSys as of the date of this release and involve known and unknown risks and uncertainties, which might cause the actual results, financial condition and liquidity, performance or achievements of MorphoSys, or industry results, to be materially different from any historic or future results, financial conditions and liquidity, performance or achievements expressed or implied by such forward-looking statements. In addition, even if MorphoSys' results, performance, financial condition and liquidity, and the development of the industry in which it operates are consistent with such forward-looking statements, they may not be predictive of results or developments in future periods. Among the factors that may result in differences are that MorphoSys' expectations may be incorrect, the inherent uncertainties associated with competitive developments, clinical trial and product development activities and regulatory approval requirements, MorphoSys' reliance on collaborations with third parties, estimating the commercial potential of its development programs and other risks indicated in the risk factors included in MorphoSys' Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. MorphoSys expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements, unless specifically required by law or regulation.