Collaborative Arrangements and Licensing Agreements

9 Months Ended

Sep. 30, 2022

Collaborative Arrangements and Licensing Agreements [Abstract]

Collaborative Arrangements and Licensing Agreements

6.  Collaborative Arrangements and Licensing Agreements

Below, we have included our Biogen, Roche and Bayer collaborations, which are our only collaborations with substantive changes during 2022 from those included in Note 6 of our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 2021.

Strategic Partnership

Biogen

We have several strategic collaborations with Biogen focused on using antisense technology to advance the treatment of neurological disorders. These collaborations combine our expertise in creating antisense medicines with Biogen’s expertise in developing therapies for neurological disorders. We developed and licensed to Biogen SPINRAZA, our approved medicine to treat people with spinal muscular atrophy, or SMA. We and Biogen are currently developing numerous investigational medicines to treat neurodegenerative diseases under these collaborations, including medicines in development to treat people with ALS, SMA, Angelman Syndrome, Alzheimer’s disease and Parkinson’s disease. In addition to these medicines, our collaborations with Biogen include a substantial research pipeline that addresses a broad range of neurological diseases. From inception through September 30, 2022, we have received $3.4 billion from our Biogen collaborations.

During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Biogen (in millions, except percentage amounts):

	Three Months Ended September 30,						Nine Months Ended September 30,
	2022			2021			2022			2021
SPINRAZA royalties (commercial revenue)	$	61.6		$	66.6		$	175.1		$	198.7
R&D revenue		27.4			17.4			84.6			63.4
Total revenue from our relationship with Biogen	$	89.0		$	84.0		$	259.7		$	262.1
Percentage of total revenue		56	%		63	%		60	%		71	%

Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021 included deferred revenue of $360.2 million and $407.5 million, respectively, related to our relationship with Biogen.

In the third quarter of 2022, we earned $13 million in milestone payments from Biogen when Biogen advanced two targets under our neurology collaborations. We recognized one of these milestone payments in full in the third quarter of 2022 because we did not have any remaining performance obligations related to the milestone payment. We added the other payment to the transaction price and allocated it to our R&D services performance obligation for the 2012 neurology collaboration. We are recognizing revenue for our R&D services performance obligation over our estimated period of performance. We will achieve the next payment of up to $10 million if Biogen advances another medicine under our 2013 strategic neurology collaboration.

Roche

We have two collaborations with Roche, one to develop IONIS-FB-L_Rx for the treatment of complement-mediated diseases, and one to develop treatments for Huntington's disease, or HD.

In October 2018, we entered into a collaboration agreement with Roche to develop IONIS-FB-L_Rx. We are currently conducting Phase 2 studies in two disease indications for IONIS-FB-L_Rx, one for the treatment of patients with geographic atrophy, or GA, the advanced stage of dry AMD, and a second for the treatment of patients with immunoglobulin A nephropathy, or IgAN. After positive data from a Phase 2 clinical study, Roche licensed IONIS-FB-L_Rx in July 2022 for $35 million and plans to advance IONIS-FB-L_Rx into Phase 3 development for patients with IgAN. As a result, Roche is responsible for global development, regulatory and commercialization activities and costs for the Phase 3 IgAN study of IONIS-FB-L_Rx. We will continue to lead and conduct the open label Phase 2 study in patients with IgAN and the Phase 2 study in patients with GA. In July 2022, we amended our IONIS-FB-L_Rx collaboration agreement with Roche. The amendment changed future potential milestone payments we could receive under the collaboration. We determined there were no changes that would require adjustments to revenue we previously recognized. Under our amended collaboration agreement, we are eligible to receive up to $145 million in development milestones, $279 million in regulatory milestones and $280 million in sales-related milestone payments. In addition, we are also eligible to receive tiered royalties from the high teens to 20 percent on net sales.

Under the collaboration agreement with Roche to develop treatments for HD, we discovered and developed tominersen, an investigational medicine targeting huntingtin, or HTT, protein, through completion of our Phase 1/2 clinical study in people with early stage HD. In the fourth quarter of 2017, upon completion of the Phase 1/2 study, Roche exercised its option to license tominersen. Roche is responsible for all global development, regulatory and commercialization activities and costs for tominersen. In March 2021, Roche decided to discontinue dosing in the Phase 3 GENERATION HD1 study of tominersen in patients with manifest HD based on the results of a pre-planned review of data from the Phase 3 study conducted by an unblinded iDMC. In January 2022, Roche announced it is actively preparing to initiate a new Phase 2 study of tominersen in patients with HD. Post-hoc analyses from the GENERATION HD1 study suggested tominersen may benefit younger adult patients with lower disease burden. From inception through September 30, 2022, we have received $283 million from our Roche collaborations.

During the three and nine months ended September 30, 2022 and 2021, we earned the following revenue from our relationship with Roche (in millions, except percentage amounts):

	Three Months Ended September 30,						Nine Months Ended September 30,
	2022			2021			2022			2021
R&D revenue	$	41.5		$	3.9		$	65.4		$	11.4
Percentage of total revenue		26	%		3	%		15	%		3	%

Our condensed consolidated balance sheet at September 30, 2022 and December 31, 2021 included deferred revenue of $23.6 million and $31.6 million, respectively, related to our relationship with Roche.

As discussed above, in the third quarter of 2022, we earned a $35 million payment from Roche when Roche licensed IONIS-FB-L_Rx. We recognized the license fee as revenue in the third quarter of 2022 because Roche had full use of the license without any continuing involvement from us. Additionally, we did not have any further performance obligations related to the license after we delivered it to Roche. We will achieve the next payment of up to $90 million if Roche advances a medicine under our IONIS-FB-L_Rx collaboration.

Bayer

In May 2015, we entered into an exclusive license agreement with Bayer to develop and commercialize IONIS-FXI_Rx for the prevention of thrombosis. In February 2017, we amended our agreement with Bayer to advance IONIS-FXI_Rx, initiate development of fesomersen, an investigational LIgand-Conjugated Antisense medicine we designed to inhibit the production of Factor XI, and license fesomersen to Bayer. In the fourth quarter of 2022, Bayer communicated to us that it will discontinue the clinical development program for fesomersen and return fesomersen to us. We have received over $190 million from Bayer over the term of this collaboration.