Amgen’s pending $28-billion acquisition of the rare-disease bio/pharmaceutical company, Horizon Therapeutics, announced this week, was one of the largest deals in 2022. What other deals stood out this year?

Rare-disease deals stood out in 2022
Mergers and acquisitions (M&A) for companies with rare-disease portfolios was a key target in 2022, with one of the largest deals coming this month (December 2022) when Amgen agreed to acquire Horizon Therapeutics, a Dublin, Ireland-based bio/pharmaceutical company focused on rare diseases, for $27.8 billion. 

Amgen was not the only suitor for Horizon. Horizon reported in late November (November 2022) that it was in preliminary discussions over a possible acquisition of the company by Amgen, Sanofi, and Johnson & Johnson (J&J). J&J reported earlier this month (December 3, 2022) that it was not bidding for the company, and Sanofi reported this week (December 11, 2022), it was no longer in discussions with Horizon and did not intend to make an offer for the company.  

Horizon has 12 marketed medicines and a pipeline with more than 20 development programs. Its top commercial product is Tepezza (teprotumumab-trbw), a drug for treating thyroid eye disease, which 2021 sales of $1.66 billion. Its second best-selling product is Krystexxa (pegloticase), a drug for treating gout, which had 2021 sales of $565 million. The company has more than 2,000 employees. The deal is expected to close in the first half of 2023, subject to receipt of Horizon shareholder approval and customary regulatory approvals.  

Amgen’s pending $28-billion acquisition of Horizon Therapeutics stands out in M&A in the pharma and biotech industry in 2022, which has seen a drop in both deal value and number of deals in 2022. Through mid-November 2022, the value of pharma and biotech M&A tallied to $137.8 billion, a 49% decrease in deal value comparative to 2021, according to a PwC analysis. The number of deals through mid-November 2022 was 266, a decrease of 28% compared to 2021.

Among the large bio/pharmaceutical companies, small to mid-sized M&A were a theme in 2022. Amgen’s pending $28-billion acquisition of Horizon Therapeutics was the second rare-disease acquisition by Amgen in 2022, the other being a much smaller deal: its $3.7-billion acquisition of ChemoCentryx. ChemoCentryx is a San Carlos, California-based bio/pharmaceutical company developing oral drugs to treat autoimmune diseases, inflammatory disorders, and cancer, primarily for orphan and rare diseases. ChemoCentryx is focused on the discovery, development, and commercialization of small-molecule therapeutics that target the chemoattractant system. Discrete chemokine or chemoattractant receptors play a specific role in how certain diseases progress. Each of its drug candidates focuses on a specific chemokine or chemoattractant receptor that blocks the negative inflammatory or suppressive response driven by that particular receptor while leaving the rest of the immune system intact.

ChemoCentryx has one commercial product, Tavneos (avacopan), a drug to treat anti-neutrophil cytoplasmic autoantibody-associated vasculitis, an umbrella term for a group of multi-system autoimmune diseases with small-vessel inflammation. In addition to Tavneos, ChemoCentryx has three early-stage drug candidates that target chemoattractant receptors in other inflammatory diseases and an oral checkpoint inhibitor for cancer.

Other deals of note in 2022
The large bio/pharmaceutical companies also made other key moves in 2022. Highlights of some of those deals are outlined below.

Pfizer’s $11.6-billion acquisition of Biohaven Pharmaceuticals. Pfizer’s $11.6-billion acquisition of Biohaven Pharmaceuticals, a New Haven, Connecticut-based bio/pharmaceutical company focused on  the treatment of migraines, was one of the largest acquisitions in 2022 aside from Amgen’s pending $28-billion acquisition of Horizon Therapeutics. Biohaven has a portfolio of calcitonin gene-related peptide receptor antagonists (CGPR), including rimegepant, which is approved in the US under the brand name Nurtec ODT and in the European Union as Vydura for the acute and preventive treatment of migraines. It was first approved in the US in 2020 for the acute treatment of migraines and as a preventive treatment in 2021 and for both indications in the EU in April 2022. Nurtec ODT (rimegepant) posted 2021 net revenues of $462.5 million. Biohaven’s other key asset is zavegepant, an intranasal spray for the acute treatment of migraines, for which a new drug application was submitted to the US Food and Drug Administration in March 2022 and which is under FDA review with a Prescription Drug User Fee Act (PDUFA) review goal date in the first quarter of 2023. An oral softgel version of zavegepant, is also under development. The company also has five preclinical programs of CGPR antagonists for treating migraines.

Pfizer’s full acquisition of Biohaven follows a $1.24-billion licensing deal by the companies, completed in January (January 2022), for the commercialization outside of the US of rimegepant, and zavegepant. Under that deal, Pizer made an upfront payment of $500 million in Biohaven and took a 3% equity stake in Biohaven with Biohaven eligible to receive up to an additional $740 million in potential milestones.

Prior to the closing of the acquisition, Biohaven spun off its non-CGRP development-stage pipeline compounds, to form a new company, Biohaven Ltd. That company’s assets include Kv7 ion channel activators, glutamate modulation and myostatin inhibition platforms, preclinical product candidates, and certain corporate infrastructure assets excluded from the Pfizer acquisition. Pfizer took a 3% stake in the new company.

Pfizer’s $5.4-billion acquisition of Global Blood Therapeutics. Pfizer also made a smaller-scale acquisition in 2022: its $5.4-billion acquisition of Global Blood Therapeutics. (GBT), a San Francisco, California-based bio/pharmaceutical company focused on sickle cell-disease. GBT’s lone commercial product is Oxbryta (voxelotor) for treating sickle-cell disease.  It was approved in the US in November 2019 and is also approved in the European Union, United Arab Emirates, Oman, and Great Britain. It had 2021 net sales of $195 million. Pfizer estimates that GBT’s pipeline and Oxbryta have the potential for a sickle-cell disease franchise that could achieve combined worldwide peak sales of more than $3 billion. Key pipeline assets of GBT are inclacumab, in Phase III development, to address pain crises associated with sickle-cell disease, and GBT021601, a sickle hemoglobin polymerization inhibitor, in Phase II of Phase II/III trials. Both products have received orphan drug and rare pediatric disease designations from the US Food and Drug Administration.

Takeda’s pending $6-billion of certain drug candidates from Nimbus Therapeutics. Although not a company acquisition, a large product acquisition comes from Takeda. Earlier this month (December 2022), Takeda  agreed to acquire a Phase II drug candidate for treating autoimmune diseases from Nimbus Therapeutics, a Cambridge, Massachusetts-based clinical-stage bio/pharmaceutical company, in a deal worth up to $6 billion ($4 billion upfront and $2 billion in milestone payments).  The drug candidate is NDI-034858, an oral, selective allosteric tyrosine kinase 2 inhibitor being evaluated for the treatment of multiple autoimmune diseases following successful recent Phase IIb results in psoriasis (as reported on December 13, 2022). NDI-034858 is anticipated to enter Phase III in psoriasis in 2023. It is in an ongoing Phase IIb study in active psoriatic arthritis, and Takeda plans to investigate it for the treatment of inflammatory bowel disease and other autoimmune diseases.  Under the agreement, Takeda will pay Nimbus $4 billion upfront and two milestone payments of $1 billion each upon NDI-034858 achieving annual net sales of $4 billion and $5 billion. The transaction is expected to be finalized before the end of 2022, subject to customary closing conditions and regulatory approval.

GSK’s $3.3-billion acquisition of Affinivax. In August (August 2022), GlaxoSmithKline (GSK) completed its acquisition of Affinivax, a Cambridge, Massachusetts-based bio/pharmaceutical company developing vaccines, in a $3.3-billion deal ($2.1 billion upfront and up to $1.2 billion in potential development milestones).

Affinivax’s most advanced vaccines are pneumococcal vaccines for which it applies its proprietary vaccine technology platform, Multiple Antigen Presenting System (MAPS). MAPS supports higher valency than conventional conjugation technologies to enable broader coverage against prevalent pneumococcal serotypes and potentially creating higher immunogenicity than current vaccines.

Affinivax’s most advanced vaccine candidate, AFX3772, is in Phase II development and includes 24 pneumococcal polysaccharides plus two conserved pneumococcal proteins (compared to up to 20 serotypes in currently approved vaccines). The FDA granted breakthrough therapy designation for AFX3772 to prevent Streptococcus pneumoniae invasive disease and pneumonia in adults 50 years old and above. Phase III trials are expected to start in the short term (as reported on May 31, 2022). Phase I/II clinical trials for pediatric use are planned to begin later this year (2022). A 30-plus valent pneumococcal vaccine candidate is also in preclinical development.

Bristol-Myers Squibb’s $3.2-billion acquisition of Turning Point Therapeutics. Another acquisition by a large bio/pharma company is 2022 was Bristol-Myers Squibb’s (BMS) $3.2-billion acquisition of Turning Point Therapeutics,  a San Diego, California-based clinical-stage bio/pharmaceutical company focused on oncology. Turning Point Therapeutics has a pipeline of investigational medicines designed to target the most common mutations associated with oncogenesis or the development of tumors. The company’s lead asset, repotrectinib, is a tyrosine kinase inhibitor targeting the ROS1 and NTRK oncogenic drivers of non-small cell lung cancer (NSCLC) and other advanced solid tumors. Repotrectinib was granted three breakthrough therapy designations from the US Food and Drug Administration. BMS says it expects repotrectinib to be approved in the US in the second half of 2023 and become a new standard of care for patients with ROS1-positive NSCLC in the first-line setting.

GlaxoSmithKline’s $1.9-billion acquisition of Sierra Oncology. GlaxoSmithKline was a large bio/pharma company making a rare-disease-focused acquisition in 2022: its $1.9-billion acquisition of Sierra Oncology, a San Mateo, California-based bio/pharmaceutical company focused on rare forms of cancer. Sierra Oncology’s lead asset is momelotinib, in Phase III trials for treating myelofibrosis, a cancer of the bone marrow impacting the normal production of blood cells, resulting in anemia. Momelotinib adds to GSK’s position in hematology, which includes Blenrep (belantamab mafodotin) for treating a certain type of multiple myeloma. 

Sumitovant Biopharma’s $1.7-billion acquisition of its remaining stake in Myovant Sciences. Earlier this year (2022), Sumitovant Biopharma, a Tokyo-based bio/pharmaceutical company and subsidiary of Sumitomo Pharma, agreed to acquire for $1.7 billion the remaining 52% stake it does not already own in Myovant Sciences, a Basel, Switzerland-based bio/pharmaceutical company. Sumitovant currently holds a 48% stake.

Formed in 2019, Sumitovant Biopharma was founded through a $3-billion strategic alliance between Roivant Sciences, a bio/pharmaceutical and healthcare company, and Sumitomo Pharma, the parent company of Sumitovant. Roivant Sciences consists of multiple wholly owned or majority-owned bio/pharmaceutical subsidiaries (so-called “Vants”), each focused on a different disease area. The company employs a “hub and spoke” model for research and development, whereby each bio/pharmaceutical subsidiary functions as an independent entity (“spoke”) using shared resources from the parent (“hub”). Other Vants consist of technology-based platforms that support the operations of the bio/pharmaceutical Vants.

Myovant Sciences, focused on women’s health and prostate cancer, was one of five bio/pharma companies for which Roivant transferred its ownership interest to Sumitomo Pharma. The others were: Urovant Sciences (urinary diseases), Enzyvant Therapeutics (pediatric rare diseases), Altavant Sciences (respiratory rare diseases) and Spirovant Sciences (genetic lung disease). Myovant’s two commercial products are Orgovyx (relugolix) for treating advanced prostate cancer, and Myfembree (relugolix, estradiol, and norethindrone acetate), used to control heavy menstrual bleeding due to uterine fibroids. The transaction for Sumitomo to acquire full ownership of Myovant Sciences is expected to close in the first quarter of 2023, subject to customary closing conditions

Novartis’ $1.5-billion acquisition of Gyroscope. In February (February 2022), Novartis completed its acquisition of Gyroscope Therapeutics, a London-based ocular gene-therapy company, in a $1.5-billion deal ($800 million upfront and up to $700 million in milestone payments). Through the acquisition, Novartis added GT005, an investigational, a one-time gene therapy currently in Phase II for treating geographic atrophy, an advanced form of dry age-related macular degeneration. Gyroscope also has several additional assets in its pipeline in early discovery for retinal diseases.

Merck’s pending $1.35-billion acquisition of Imago BioSciences. In November (November 2022), Merck & Co. agreed to acquire Imago BioSciences, a Redwood City, California-based clinical-stage bio/pharmaceutical company specializing in treating rare bone-marrow diseases, for $1.35 billion.  Imago is focused on developing new medicines for treating bone-marrow diseases, including myeloproliferative neoplasms, a group of diseases of the bone marrow characterized by excessive production of red blood cells, platelets, or certain white blood cells. The deal is expected to close in the first quarter of 2023.

Imago’s lead candidate is bomedemstat (IMG-7289), in multiple Phase II clinical trials for treating several bone-marrow-diseases: essential thrombocythemia, a rare blood disorder in which the bone produces too marrow many platelets; myelofibrosis, a rare type of blood cancer characterized by the buildup of scar tissue in the bone marrow; and polycythemia vera, a type of blood cancer in which the bone marrow produces too many red blood cells.

AstraZeneca’s $1.3-billion acquisition of TeneoTwo. In August (August 2022), AstraZeneca completed its acquisition of TeneoTwo, a bio/pharmaceutical company, in a deal worth up to $1.3 billion ($100 million upfront, up to $805 million in additional contingent R&D-related milestone payments, and up to $360 million in additional contingent commercial-related milestone payments).

TeneoTwo’s key asset is TNB-486, currently in Phase I development for treating relapsed and refractory B-cell non-Hodgkin lymphoma. TNB-486 belongs to a class of therapeutic antibodies known as T-cell engagers, which are emerging as a promising therapeutic approach in hematologic malignancies and solid tumors. T-cell engagers are bispecific molecules that are engineered to redirect the immune system’s T-cells to recognize and kill cancer cells. By binding to both CD19, an antigen expressed on B-cells, and to the CD3 receptor on T-cells, TNB-486 activates and recruits T-cells to CD19-expressing tumors where they can elicit an immune response, according to information from AstraZeneca. The acquisition adds to AstraZeneca’s position in developing drugs to treat blood cancers, including B-cell hematologic malignancies, including diffuse large B-cell lymphoma and follicular lymphoma.

Sanofi’s $1.2-billion acquisition of Amunix. In February (February 2022), Sanofi completed its acquisition of Amunix Pharmaceuticals, an immuno-oncology company, in a deal worth up to $1.2-billion ($1 billion at closing plus $225 million in milestones). Amunix is developing masked T cell engagers and cytokines, which are designed to preferentially activate in the tumor microenvironment and to overcome toxicity challenges of other T cell and cytokine therapies. The company’s initial product candidate is AMX-818, a T cell engager targeting a variety of HER2-expressing solid tumors.

Novo Nordisk’s $1.1-billion acquisition of Forma Therapeutics. Another deal in rare diseases in 2022 was Novo Nordisk’s $1.1-billion acquisition of Forma Therapeutics, a Watertown, Massachusetts-based clinical-stage bio/pharmaceutical company focused on sickle-cell disease and rare blood disorders. Forma’s lead product is etavopivat, an investigational oral, once-daily drug being developed to improve anemia and red-blood cell health in people with sickle-cell disease. Etavopivat is being evaluated in a global Phase II/III clinical trial in patients with sickle-cell disease and in a Phase II trial in patients with transfusion-dependent sickle-cell disease and thalassemia, an inherited blood disorder that results in lower hemoglobin levels than normal.

AbbVie’s $1-billion acquisition of Syndesi Therapeutics. To enhance its neuroscience portfolio, in March (March 2022), AbbVie acquired Syndesi Therapeutics, a Belgium-based bio/pharmaceutical company, in a $1-billion deal ($130 million upfront and up to $870 million in milestone payments). Syndesi is focused on developing therapeutics that modulate synaptic function to relieve the symptoms of cognitive impairment. Syndesi’s molecules act pre-synaptically to enhance synaptic efficiency by positively modulating the function of the synaptic vesicle protein 2A (SV2A), which plays a role in regulating neurotransmission. The acquisition gives AbbVie access to Syndesi’s portfolio of modulators of SV2A, including Syndesi’s lead molecule, SDI-118, a small-molecule drug currently in Phase Ib studies, which is being evaluated to target nerve terminals to enhance synaptic efficiency. Synaptic dysfunction is believed to underlie the cognitive impairment seen in multiple neuropsychiatric and neurodegenerative disorders